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Aims General anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating. Methods Immunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst‐suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods. Results We found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5‐HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5‐HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons. Conclusion Our results demonstrate that 5‐HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5‐HT 1A and 2C receptors., General anesthesia decreases the activities of serotonergic neurons in the dorsal raphe. Activation of DRN 5‐HT neurons reduced the depth of anesthesia and accelerated the emergence from general anesthesia, partially through the 5‐HT 1A and 2C receptors.

The development of whole slide imaging techniques and online digital pathology platforms have accelerated the popularization of telepathology for remote tumor diagnoses. During a diagnosis, the behavior information of the pathologist can be recorded by the platform and then archived with the digital case. The browsing path of the pathologist on the WSI is one of the valuable information in the digital database because the image content within the path is expected to be highly correlated with the diagnosis report of the pathologist. In this article, we proposed a novel approach for computer-assisted cancer diagnosis named session-based histopathology image recommendation (SHIR) based on the browsing paths on WSIs. To achieve the SHIR, we developed a novel diagnostic regions attention network (DRA-Net) to learn the pathology knowledge from the image content associated with the browsing paths. The DRA-Net does not rely on the pixel-level or region-level annotations of pathologists. All the data for training can be automatically collected by the digital pathology platform without interrupting the pathologists’ diagnoses. The proposed approaches were evaluated on a gastric dataset containing 983 cases within 5 categories of gastric lesions. The quantitative and qualitative assessments on the dataset have demonstrated the proposed SHIR framework with the novel DRA-Net is effective in recommending diagnostically relevant cases for auxiliary diagnosis. The MRR and MAP for the recommendation are respectively 0.816 and 0.836 on the gastric dataset. The source code of the DRA-Net is available at https://github.com/zhengyushan/dpathnet .

Colorectal carcinoma (CRC) is a major type of malignancy worldwide. Ellagic acid (EA), a natural phenolic constituent, has been shown to exhibit anticancer effects. In our previous study, it was shown that EA inhibited proliferation of CRC cells. Additionally, microarray analysis revealed 4,738 differentially expressed genes (DEGs) which were associated with multiple cellular events, including cell growth, apoptosis and angiogenesis. However, the associated pathways had not been validated. In the present study, it was shown that EA induced G0/G1 cell cycle arrest in HCT‑116 cells, and increased apoptosis. Furthermore, DEGs identified by cDNA microarray analysis were investigated, and showed changes in five genes which were associated with the TGF‑β1/Smad3 signaling pathway. TGF‑β1 small interfering RNA and SIS3, a Smad3 inhibitor, were used to assess the role of TGF‑β1 and Smad3, respectively, and it was shown that the they reduced the effects of EA on HCT‑116 CRC cells. In addition, the expression patterns of downstream DEGs of the TGF‑β1/Smad3 pathway were altered. Thus, this pathway may underlie the molecular mechanism by which EA exhibits its effects in vitro in CRC cells. Accordingly, targeting the TGF‑β1/Smad3 pathway with anticancer agents such as EA may be potentially used to treat CRC.

BACKGROUND AND PURPOSE The utility of non-contrast computed tomography (NCCT) markers in the prognosis of spontaneous intracerebral hemorrhage (ICH) has been concerned. This study aimed to investigate the predictive value of the computed tomography irregularity shape for poor functional outcomes in patients with spontaneous intracerebral hemorrhage. PATIENTS AND Methods: We retrospectively reviewed all 782 patients with intracranial hemorrhage in our stroke emergency center from January 2018 to September 2019. Laboratory examination and CT examination were measured within 24 hours of admission. After three months, the patient's functional outcome was assessed using the modified Rankin Scale (mRS). Multinomial logistic regression analyses were applied to identify independent predictors of functional outcome in patients with intracerebral hemorrhage. RESULTS Out of the 627 patients included in this study, those with irregular shapes on CT imaging had a higher proportion of poor outcome and mortality 90 days after discharge (P

Purpose: The study seeks to utilise the extensively monitored data to explore the prognostic information in the continuous ambulatory vital signs of the pregnant women with pulmonary hypertension in the ICU, aiming to bring insights to physicians on evaluation and management of these specific patients. Methods: This is a retrospective study of consecutive obstetric patients with PH admitted to ICU of the First Affiliated Hospital of Air Force Military Medical University of China, from January 2011 to May 2020. 92 cases are analysed via time-dependent Cox regression to take account of the dynamic features of vital signs. Results: Seven out of 92 maternal deaths occurred, with most maternal deaths occurring within the first three days of admission to the ICU. The vital signs for the survived are more stable and normally ranged comparing to the death. Three vital signs are identified as risk factors in the maternal in-hospital mortality model: SpO 2 (OR,0.93;95%CI,0.89-0.98), Heart rate(OR, 0.95 ; 95%CI, 0.92-0.99), Mean blood pressure(OR, 1.1 ; 95%CI, 0.98-1). The model performance is justified by the ROC curve with AUC being 0.84. Further exploration showed that the total and the longest consecutive time ratios also affect the outcome. Conclusions: Pregnancy women with PH who dead in hospital experienced long-term abnormal fluctuations in blood pressure, heart rate and blood oxygen during ICU stay. Both dynamic and time ratios reported impacts relating to SpO 2 , heart rate and blood pressure. In general SpO 2 mitigate the hazard. Effects of the heart rate and mean blood pressure should be described combining the time ratios of hypotension and tachycardia.

Background Psoriasis is a common chronic inflammatory skin disease that causes physical and psychological burden to patients. A Convolutional Neural Network (CNN) focused on dermoscopic images would substantially aid the classification and increase the accuracy of diagnosis of psoriasis. Objectives This study aimed to train an efficient deep-learning network to recognize dermoscopic images of psoriasis (and other papulosquamous diseases), improving the accuracy of the diagnosis of psoriasis. Methods EfficientNet-B4 architecture was trained with 7033 dermoscopic images from 1166 patients collected from the Department of Dermatology, Peking Union Medical College Hospital (China). We performed a five-fold cross-validation on the training set to compare the classification performance of EfficientNet-B4 over different networks commonly used in previous studies. From the test set, 90 images were used to compare the performance between our four-class model and that of board-certified dermatologists, whose diagnoses and information (e.g., age, titles) were obtained through an online questionnaire. Results The mean sensitivity and specificity of EfficientNet-B4 on the training set was 0.927 ± 0.028 and 0.827 ± 0.043 for the two-class task, and 0.889 ± 0.014 and 0.968 ± 0.004 four-class task. The diagnostic sensitivity and specificity of the 230 dermatologists were 0.688 and 0.903 for psoriasis, 0.677 and 0.838 for eczema, 0.669 and 0.953 for lichen planus, and 0.832 and 0.932 for the “others” group, respectively; the diagnostic sensitivity and specificity of our four-class CNN was 0.929 and 0.952 for psoriasis, 0.773 and 0.926 for eczema, 0.933 and 0.960 for lichen planus, and 0.840 and 0.985 for the “others” group, respectively. Both the 230 dermatologists and CNN achieved at least moderate consistency with the reference standard, and there was no significant difference between them (P > 0.05). Conclusions The two-classification and four-classification models of psoriasis established in our study could accurately classify papulosquamous skin diseases. They showed generally comparable performances to the average level of dermatologists and would provide a strong support for the diagnosis of psoriasis.

Background. Colorectal cancer (CRC) is among the top three gastrointestinal malignancy in morbidity and mortality. The abnormal activation of Wnt/β-catenin pathway is considered to be a key factor in the occurrence and development of CRC. Novel inhibitor discovery against key factor in WNT pathway is important for CRC treatment and prevention. Methods. Cell proliferation was detected after hydroxyphenyl butanone treatment in human colorectal cancer HCT116, LOVO, and normal colonic epithelial NCM460 cells. Colony formation, cell invasion ability, and cell cycle were detected with and without GSK-3β knockdown. Results. Hydroxyphenyl butanone induces cycle arresting on G1-S phase of colorectal cancer cell line through GSK3β in Wnt/β-catenin pathway and inhibits malignant biological manifestations of cell proliferation, colony formation, and invasion. The inhibition in the high concentration group is stronger than that in the low concentration group, and the antitumor effect is different for different tumor cells. Under the same concentration of natural hydroxyphenyl butanone, the inhibition on normal colonic epithelial cells is significantly lower than that on tumor cells. The natural hydroxyphenyl butanone with medium and low concentration could promote the proliferation of normal colonic epithelial cells. Conclusion. This study illustrated natural hydroxyphenyl butanone as new inhibitor of GSK3β and revealed the mechanisms underlying the inhibitory effects in colorectal cancer.

Automatic segmentation of histopathological whole slide images (WSIs) is challenging due to the high resolution and large scale. In this paper, we proposed a cascade strategy for fast segmentation of WSIs based on convolutional neural networks. Our segmentation framework consists of two U-Net structures which are trained with samples from different magnifications. Meanwhile, we designed a novel cancer sensitive loss (CSL), which is effective in improving the sensitivity of cancer segmentation of the first network and reducing the false positive rate of the second network. We conducted experiments on ACDC-LungHP dataset and compared our method with 2 state-of-the-art segmentation methods improved from U-Net. The experimental results have demonstrated that the proposed method can improve the segmentation accuracy and meanwhile reduce the amount of computation. The dice score coefficient and precision of lung cancer segmentation are 0.694 and 0.947, respectively, which are superior to the compared methods.

Pedestal looseness and supporting stiffness nonlinearities usually occur in rotating machines. To enhance the robustness and accurately forecast the nonlinear behaviors of rotor systems, these two kinds of common nonlinearities should be considered so that to meet the requirements of the dynamical design of a multi-disk rotor system. In this paper, the rotor system model with cubic supporting stiffness and looseness fault is established by the Lagrange method. The harmonic balance (HB) and Runge–Kutta (RK) methods are used to solve the dynamic response of the double disk rotor system, and the accuracy of the HB method is justified in comparison to the RK method. The bifurcation diagram, time history, frequency spectrum, phase portrait and Poincare map are provided to discuss the individual and coupling effects of these two nonlinearities on the transient and steady-state response. The obtained experimental results indicate that the proposed model can capture the main nonlinear behaviors of looseness fault and nonlinear supporting stiffness, verifying the accuracy of theoretical and numerical results.

Feature extraction is a crucial and challenging aspect in the computer-aided diagnosis of breast cancer with histopathological images. In recent years, many machine learning methods have been introduced to extract features from histopathological images. In this study, a novel nucleus-guided feature extraction framework based on convolutional neural network is proposed for histopathological images. The nuclei are first detected from images, and then used to train a designed convolutional neural network with three hierarchy structures. Through the trained network, image-level features including the pattern and spatial distribution of the nuclei are extracted. The proposed features are evaluated through the classification experiment on a histopathological image database of breast lesions. The experimental results show that the extracted features effectively represent histopathological images, and the proposed framework achieves a better classification performance for breast lesions than the compared state-of-the-art methods.

Telepathology has enabled the remote cancer diagnosis based on digital pathological whole slide images (WSIs). During the diagnosis, the behavior information of the pathologist can be recorded by the platform and then archived with the digital cases. The diagnosis path of the pathologist on a WSI is valuable information since the image content within the path is highly correlated with the diagnosis report of the pathologist. In this paper, we proposed a novel diagnosis path network (DPathNet). DPathNet utilizes the diagnosis paths of pathologists on the WSIs as the supervision to learn the pathology knowledge from the image content. Based on the DPathNet, we develop a novel approach for computer-aided cancer diagnosis named session-based histopathology image recommendation (SHIR). SHIR summaries the information of a WSI while the pathologist browsing the WSI and actively recommends the relevant cases within similar image content from the database. The proposed approaches are evaluated on a gastric dataset containing 983 cases within 5 categories of gastric lesions. The experimental results have demonstrated the effectiveness of the DPathNet to the SHIR task and the supervision of the diagnosis path is sufficient to train the DPathNet. The MRR and MAP of the proposed SHIR framework are respectively 0.741 and 0.777 on the gastric dataset.

The frequent hazy weather with air pollution in North China has aroused wide attention in the past few years. One of the most important pollution resource is the anthropogenic emission by fossil-fuel power plants. To relieve the pollution and assist urban environment monitoring, it is necessary to continuously monitor the working status of power plants. Satellite or airborne remote sensing provides high quality data for such tasks. In this paper, we design a power plant monitoring framework based on deep learning to automatically detect the power plants and determine their working status in high resolution remote sensing images (RSIs). To this end, we collected a dataset named BUAA-FFPP60 containing RSIs of over 60 fossil-fuel power plants in the Beijing-Tianjin-Hebei region in North China, which covers about 123 km 2 of an urban area. We compared eight state-of-the-art deep learning models and comprehensively analyzed their performance on accuracy, speed, and hardware cost. Experimental results illustrate that our deep learning based framework can effectively detect the fossil-fuel power plants and determine their working status with mean average precision up to 0.8273, showing good potential for urban environment monitoring.

Histopathological image classification (HIC) and content-based histopathological image retrieval (CBHIR) are two promising applications for the histopathological whole slide image (WSI) analysis. HIC can efficiently predict the type of lesion involved in a histopathological image. In general, HIC can aid pathologists in locating high-risk cancer regions from a WSI by providing a cancerous probability map for the WSI. In contrast, CBHIR was developed to allow searches for regions with similar content for a region of interest (ROI) from a database consisting of historical cases. Sets of cases with similar content are accessible to pathologists, which can provide more valuable references for diagnosis. A drawback of the recent CBHIR framework is that a query ROI needs to be manually selected from a WSI. An automatic CBHIR approach for a WSI-wise analysis needs to be developed. In this paper, we propose a novel aided-diagnosis framework of breast cancer using whole slide images, which shares the advantages of both HIC and CBHIR. In our framework, CBHIR is automatically processed throughout the WSI, based on which a probability map regarding the malignancy of breast tumors is calculated. Through the probability map, the malignant regions in WSIs can be easily recognized. Furthermore, the retrieval results corresponding to each sub-region of the WSIs are recorded during the automatic analysis and are available to pathologists during their diagnosis. Our method was validated on fully annotated WSI data sets of breast tumors. The experimental results certify the effectiveness of the proposed method.

The red raspberry (Rubus idaeus L.) is a common fruit worldwide and its extract has been found to inhibit the growth of many types of tumors, mainly because it is rich in bioactive phytochemicals. However, the mechanism underlying its anticancer activity in hepatocellular carcinoma (HCC) is not well understood. Herein, the aim of this study was to determine the effects of red raspberry phytochemicals on the proliferation of hepatocellular carcinoma cells and to elucidate its biochemical and molecular targets. CCK8 and colony formation, as well as flow cytometry assays, were employed to determine the effects of red raspberry extract (RRE) on cell proliferation and cell cycle distribution in HCC cells. Our results showed that RRE significantly inhibited cell proliferation and arrested cell cycle progression at the S phase in HCC cells. RRE increased the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) by reducing the methylation status of the PTEN gene promoter and inhibiting DNMT1 expression and regulated AKT signaling pathway. These findings show that red raspberry phytochemicals inhibit the proliferation of HCC cells by regulating PTEN/AKT signaling pathway, providing evidence that RRE may be used as a potential auxiliary therapy for patients with HCC.

Neurotensin (NT) serves as a neuromodulator in the brain where it is involved in modulating a variety of physiological functions including nociception, temperature, blood pressure and cognition, and many neurological diseases such as Alzheimer's disease, schizophrenia and Parkinson's disease. Whereas there is compelling evidence demonstrating that NT facilitates cognitive processes, the underlying cellular and molecular mechanisms have not been fully determined. Because the dentate gyrus expresses high densities of NT and NT receptors, we examined the effects of NT on the synaptic transmission at the synapse formed between the perforant path (PP) and granule cells (GC) in the rats. Our results demonstrate that NT persistently increased the amplitude of the AMPA receptor-mediated EPSCs at the PP-GC synapse. NT-induced increases in AMPA EPSCs were mediated by presynaptic NTS1 receptors. NT reduced the coefficient of variation and paired-pulse ratio of AMPA EPSCs suggesting that NT facilitates presynaptic glutamate release. NT increased the release probability and the number of readily releasable vesicles with no effects on the rate of recovery from vesicle depletion. NT-mediated augmentation of glutamate release required the influx of Ca(2+) via L-type Ca(2+) channels and the functions of calmodulin and myosin light chain kinase. Our results provide a cellular and molecular mechanism to explain the roles of NT in the hippocampus.

Loss of dopaminergic (DA) neurons leads to Parkinson's disease; however, the mechanism(s) for the vulnerability of DA neurons is(are) not fully understood. We demonstrate that TRPC1 regulates the L-type Ca2+channel that contributes to the rhythmic activity of adult DA neurons in the substantia nigra region. Store depletion that activates TRPC1, via STIM1, inhibits the frequency and amplitude of the rhythmic activity in DA neurons of wild-type, but not in TRPC1−/−, mice. Similarly, TRPC1−/−substantia nigra neurons showed increased L-type Ca2+currents, decreased stimulation-dependent STIM1-Cav1.3 interaction, and decreased DA neurons. L-type Ca2+currents and the open channel probability of Cav1.3 channels were also reduced upon TRPC1 activation, whereas increased Cav1.3 currents were observed upon STIM1 or TRPC1 silencing. Increased interaction between Cav1.3-TRPC1-STIM1 was observed upon store depletion and the loss of either TRPC1 or STIM1 led to DA cell death, which was prevented by inhibiting L-type Ca2+channels. Neurotoxins that mimic Parkinson's disease increased Cav1.3 function, decreased TRPC1 expression, inhibited Tg-mediated STIM1-Cav1.3 interaction, and induced caspase activation. Importantly, restoration of TRPC1 expression not only inhibited Cav1.3 function but increased cell survival. Together, we provide evidence that TRPC1 suppresses Cav1.3 activity by providing an STIM1-based scaffold, which is essential for DA neuron survival.SIGNIFICANCE STATEMENTCa2+entry serves critical cellular functions in virtually every cell type, and appropriate regulation of Ca2+in neurons is essential for proper function. In Parkinson's disease, DA neurons are specifically degenerated, but the mechanism is not known. Unlike other neurons, DA neurons depend on Cav1.3 channels for their rhythmic activity. Our studies show that, in normal conditions, the pacemaking activity in DA neurons is inhibited by the TRPC1-STIM1 complex. Neurotoxins that mimic Parkinson's disease target TRPC1 expression, which leads to an abnormal increase in Cav1.3 activity, thereby causing degeneration of DA neurons. These findings link TRPC1 to Cav1.3 regulation and provide important indications about how disrupting Ca2+balance could have a direct implication in the treatment of Parkinson's patients.

Content-based image retrieval (CBIR) has been widely researched for medical images. In application of histo- pathological images, there are two issues that need to be carefully considered. The one is that the digital slide is stored in a spatially continuous image with a size of more than 10K x 10K pixels. The other is that the size of query image varies in a large range according to different diagnostic conditions. It is a challenging work to retrieve the eligible regions for the query image from the database that consists of whole slide images (WSIs). In this paper, we proposed a CBIR framework for the WSI database and size-scalable query images. Each WSI in the database is encoded and stored in a matrix of binary codes. When retrieving, the query image is first encoded into a set of binary codes and analyzed to pre-choose a set of regions from database using hashing method. Then a multi-binary-code-based similarity measurement based on hamming distance is designed to rank proposal regions. Finally, the top relevant regions and their locations in the WSIs along with the diagnostic information are returned to assist pathologists in diagnoses. The effectiveness of the proposed framework is evaluated in a fine-annotated WSIs database of epithelial breast tumors. The experimental results show that proposed framework is both effective and efficiency for content-based whole slide image retrieval.

Preconditioning with volatile anesthetics can create an ischemia tolerance against cerebral ischemia-reperfusion injury. We investigated whether ubiquitin conjugase 9 (Ubc9), the E2 conjugase for SUMOylation, is associated with neuroprotection induced by isoflurane preconditioning (IsoPC). In vitro, Ubc9 protein expression was evaluated at 4 and 24 h after reoxygenation. The role of Ubc9 in the neuroprotective effect was assessed in the presence or absence of Ubc9 small interfering RNA (siRNA). In vivo, rats were preconditionally exposed for 1 h to 2 % isoflurane for five consecutive days followed by middle cerebral artery occlusion. Neurobehavioral scores and infarction volume were determined at different times after reperfusion. The role of Ubc9 in ischemic tolerance was evaluated by intracerebroventricular microinjection with the Ubc9 siRNA. We showed that isoflurane preconditioning improved the cell viability of the SH-SY5Y cells that were challenged by oxygen-glucose deprivation. It also reduced brain infarct volumes and improved neurologic outcomes in the focal cerebral ischemic rat. The expression of Ubc9 was upregulated by isoflurane preconditioning. Knockdown of Ubc9 significantly attenuated the isoflurane preconditioning-induced neuroprotective effects. Isoflurane preconditioning-induced neuroprotection against ischemic injuries is mediated by Ubc9. These results suggest a novel mechanism for isoflurane preconditioning-induced tolerance to cerebral ischemia.

The neuroprotective properties for certain medical gases have been observed for decades, leading to extensive research that has been widely reported and continues to garner interest. Common gases including oxygen, hydrogen, carbon dioxide and nitric oxide, volatile anesthetics such as isoflurane, sevoflurane, halothane, enflurane and desflurane, non-volatile anesthetics such as xenon and nitrous oxide, inert gases such as helium and argon, and even gases classically considered to be toxic (e.g., hydrogen sulfide and carbon monoxide) have all been supported by the evidence alluding to their use as potential neuroprotective agents. A wide range of neural injury types such as ischemic/hemorrhagic, stroke, subarachnoid hemorrhage, traumatic brain injury, perinatal hypoxic-ischemic brain injuries, neurodegenerative disease as well as spinal cord ischemia have been used as platforms for studying the neuroprotective effects of these gases, yet until now, none of the gases has been widely introduced into clinical use specifically for protection against neural injury. Insufficient clinical data together with contradictory paradigms and results further hinders the clinical trials. However, pre-clinical models suggest that despite the various classes of gases and the broad range of injuries to which medical gases confer, protection, several underlying mechanisms for their neuroprotective properties are similar. In this review, we summarize the literature concerning the neuroprotective effect of each gas and its underlying mechanisms, extract common targets reported for the neuroprotective effects of different gases, highlight the conflicting observations from clinical trials and further discuss the possible hindrances impeding clinical applications in order to propose future research perspectives and therapeutic exploitations.

Inhalational anesthetic preconditioning can induce neuroprotective effects, and the notch signaling pathway plays an important role in neural progenitor cell differentiation and the inflammatory response after central nervous system injury. This study evaluated whether the neuroprotective effect of isoflurane preconditioning is mediated by the activation of the notch signaling pathway. Mice were divided into two groups consisting of those that did or did not receive preconditioning with isoflurane. The expression levels of notch-1, notch intracellular domain (NICD), and hairy and enhancer of split (HES-1) were measured in mice subjected to transient global cerebral ischemia-reperfusion injury. The notch signaling inhibitor DAPT and conditional notch-RBP-J knockout mice were used to investigate the mechanisms of isoflurane preconditioning-induced neuroprotection. Immunohistochemical staining, real-time polymerase chain reaction assays, and Western blotting were performed. Isoflurane preconditioning induced neuroprotection against global cerebral ischemia. Preconditioning up-regulated the expression of notch-1, HES-1, and NICD after ischemic-reperfusion. However, these molecules were down-regulated at 72 h after ischemic-reperfusion. The inhibition of notch signaling activity by DAPT significantly attenuated the isoflurane preconditioning-induced neuroprotection, and similar results were obtained using notch knockout mice. Our results demonstrate that the neuroprotective effects of isoflurane preconditioning are mediated by the pre-activation of the notch signaling pathway.

Summary Background: Foreign body aspiration is a common life-threatening event in young children. Tracheobronchial foreign body removal is usually performed by rigid tracheobronchoscopy under general anesthesia. Anesthetic and ventilation techniques vary greatly among anesthesiologists and institutions. In the present retrospective study, we report our anesthetic experience over 5 years. We describe complications and outcomes and analyze the clinical characteristics of anesthesia and ventilation. Methods: We retrospectively reviewed relevant clinical findings of 586 pediatric patients treated with rigid tracheobronchoscopy under general anesthesia. All procedures were performed under inhaled sevoflurane anesthesia combined with remifentanil infusion, with spontaneous respiration assisted by high-frequency jet ventilation (HFJV) and topical airway anesthesia. Results: Among 586 patients, the foreign body was successfully removed by rigid tracheobronchoscopy in 558 patients, and no foreign body was found in 28 patients. Laryngospasm was observed during the procedure in five patients. Hypoxemia was observed in 15 patients (2.6%). No severe complications or deaths occurred. The mean operation time was 22 min and the average hospital stay was 2 days. Conclusion: Inhaled sevoflurane anesthesia combined with remifentanil infusion, with spontaneous respiration assisted by HFJV and topical airway anesthesia, is safe and effective for tracheobronchial foreign body removal.

The aim of this study is to examine the role of one of the two-pore (2P) domain K(+) channels, TREK (TWIK-related K(+) channels, TREK)-1, mediated neuroprotection on spinal cord afforded by isoflurane preconditioning. In Experiment 1, male Sprague-Dawley rats were randomly assigned to control (Con) group, an isoflurane preconditioning (Iso) group, and sham group. Twenty-four hours after the last pretreatment, spinal cord ischemia was induced in Con and Iso groups. Neurobehavioral testing and histopathologic examination were performed after reperfusion. In Experiment 2, the expression of the TREK1 in the spinal cord was assessed by immunohistochemistry, Western blot and real-time polymerase chain reaction. In Experiment 3, Amiloride, a blocker of stretch-sensitive channels, was administered intraperitoneally immediately prior to each isoflurane preconditioning. Iso group showed a significant reductions in motor deficit index as well as increases in the number of normal neurons compared with the Con group. The expression of TREK1 protein and the level of mRNA after ischemia were higher in the rats of the Iso group than those in the Con group. Amiloride pretreatment abolished the protective effects of Iso preconditioning. These finding indicate that isoflurane preconditioning had a neuroprotective effect against spinal cord ischemia reperfusion injury. These effects may be mediated through the TREK1 pathway.

Our previous studies have demonstrated that hyperbaric oxygen (HBO) preconditioning induces tolerance to focal cerebral ischemia. The present study aimed to investigate whether autophagy is involved in the neuroprotection elicited by HBO preconditioning in a rat model of transient focal cerebral ischemia. Twenty-four hours after the completion of HBO preconditioning (2.5 atm absolute in 100% oxygen for 60 min per day for 5 consecutive days), male Sprague-Dawley rats were subjected to focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 120 min. The neurobehavioral score and infarct volume were used to evaluate cerebral ischemic injury. An intracerebroventricular injection of the autophagy inhibitor 3-methyladenine (3-MA) or the autophagy inducer rapamycin was administered before HBO preconditioning or MCAO. We found that after reperfusion the protein expression of LC3-II and Beclin 1 and the formation of autophagosomes were increased by HBO preconditioning or ischemia, but the increase following HBO preconditioning was higher than the increase following ischemia. 3-MA suppressed the increases in LC3-II and Beclin 1 induced by HBO preconditioning and attenuated the neuroprotection of HBO preconditioning against cerebral ischemia. Furthermore, 3-MA treatment before MCAO aggravated subsequent cerebral ischemic injury. In contrast, pretreatment with rapamycin up-regulated LC3-II and Beclin 1 after reperfusion and mimicked the neuroprotective effect of HBO preconditioning. These results indicate that HBO preconditioning elevates autophagic activity, which elicits a neuroprotective effect against ischemic injury in the brain, and suggest a novel mechanism of HBO preconditioning-induced tolerance against transient focal cerebral ischemia.

BACKGROUND: In this study, we sought to clarify the role of inhibiting ubiquitin-conjugated protein aggregation in the formation of a neuroprotective effect after isoflurane preconditioning using a transient global cerebral ischemia-reperfusion injury mouse model. METHODS: C57BL/6 mice were randomly assigned to 3 groups (isoflurane preconditioning [IsoPC] group, control [Con] group, and sham group, n = 24 in each group). Mice in the IsoPC group and sham group were placed in a chamber and pretreated with isoflurane (1.2% isoflurane, 98% O 2 , 1 hour/day) for 5 days. Mice in the Con group were placed in the same chamber but pretreated with oxygen only (98% O 2 , 2% N 2 , 1 hour/day) for 5 days. Twenty-four hours after the last preconditioning day, bilateral common carotid artery occlusion was performed as a model of global cerebral ischemia for 20 minutes in the IsoPC group and Con group. The total motor scores, number of viable neurons in the CA1 region of the hippocampus, and expression levels of conjugated ubiquitin or free ubiquitin were assessed by neurological assessment, immuno-histochemistry, and Western blotting (at 24 and 72 hours) after reperfusion, respectively. RESULTS: The total motor scores in the IsoPC group were better than the Con group (P < 0.05). Morphological observations showed that the IsoPC group had better neuron structure than in the Con group. The numbers of viable neurons in the CA1 region were significantly increased by isoflurane preconditioning compared with those in the Con group (P < 0.05). The numbers of TUNEL-positive neurons in the CA1 region were significantly decreased after isoflurane preconditioning. The density of conjugated ubiquitin staining in the CA1 region of the IsoPC group was significantly lower than in the Con group (P < 0.05) and the expression of conjugated ubiquitin in the IsoPC group was lower than in the Con group (P < 0.05). CONCLUSION: Inhibition of ubiquitin-conjugated protein aggregation may have an essential role in inducing cerebral ischemic tolerance by isoflurane preconditioning in a transient global cerebral ischemia-reperfusion injury mouse model.

Neurotensin (NT) is a 13-amino acid peptide and serves as a neuromodulator in the brain. Whereas NT has been implicated in learning and memory, the underlying cellular and molecular mechanisms are ill-defined. Because the dentate gyrus receives profound innervation of fibers containing NT and expresses high density of NT receptors, we examined the effects of NT on the excitability of dentate gyrus granule cells (GCs). Our results showed that NT concentration dependently increased action potential (AP) firing frequency of the GCs by the activation of NTS1 receptors resulting in the depolarization of the GCs. NT-induced enhancement of AP firing frequency was not caused indirectly by releasing glutamate, GABA, acetylcholine, or dopamine, but due to the inhibition of TASK-3 K(+) channels. NT-mediated excitation of the GCs was G protein dependent, but independent of phospholipase C, intracellular Ca(2+) release, and protein kinase C. Immunoprecipitation experiment demonstrates that the activation of NTS1 receptors induced the association of Gαq/11 and TASK-3 channels suggesting a direct coupling of Gαq/11 to TASK-3 channels. Endogenously released NT facilitated the excitability of the GCs contributing to the induction of long-term potentiation at the perforant path-GC synapses. Our results provide a cellular mechanism that helps to explain the roles of NT in learning and memory.

Ischemic stroke is one of the leading causes of mortality and disability worldwide. Our previous studies have shown that hyperbaric oxygen (HBO) preconditioning can afford significant neuroprotection against cerebral ischemia-reperfusion (I/R) injury in rats. However, it is still unknown whether HBO preconditioning can directly protect primary cultured cortical neurons against oxygen-glucose deprivation (OGD). Peroxisome proliferator-activated receptor-gamma (PPAR γ) plays a central role in the regulation of apoptosis, oxidative stress and inflammation as well as affords significant neuroprotection against cerebral I/R injury. 15-deoxy-∆(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an endogenous ligand with a high affinity for PPAR γ. Recently, some studies demonstrate that activation of PPAR γ mediates lipopolysaccharide and anesthetic preconditioning. In the present study, we firstly found that OGD exposure caused the significant damage of cultured cortical neurons evaluated by cell viability, lactate dehydrogenase (LDH) release and caspase-3 activity, which were significantly ameliorated by HBO preconditioning. Furthermore, HBO preconditioning significantly increased the levels of PPAR γ mRNA and protein, PPAR γ DNA binding activity, 15d-PGJ(2) and antioxidant enzymatic activities in primary cultured cortical neurons with OGD exposure. Moreover, PPAR γ antagonist GW9662 dose-dependently abolished the protection of HBO preconditioning in OGD-exposed neurons. GW9662 blocked the increase of PPAR γ DNA binding activity and antioxidant enzymatic activities, but did not influence the 15d-PGJ(2) level in OGD-exposed neurons with HBO preconditioning. However, the cyclooxygenase (COX)-2 inhibitor NS-398 blocked the production of 15d-PGJ(2) in OGD-exposed neurons with HBO preconditioning. In addition, 15d-PGJ(2) preconditioning could also protect cultured neurons against OGD injury. These results demonstrate that HBO preconditioning has directly beneficial effects on ODG-exposed cortical neurons by the activation of PPAR γ subsequent to the production of 15d-PGJ(2), which in turn increases the downstream antioxidant enzymatic activities.

Background Recent studies suggest that the novel neuropeptide orexin-A may play an essential role during neuronal damage. However, the function of orexin-A during brain ischemia remains unclear. Recently, hypoxia-inducible factor-1α (HIF-1α) was shown to be activated by orexin-A. The aim of the current study is to test the hypothesis that administration of exogenous orexin-A can attenuate ischemia-reperfusion injury through the facilitation of HIF-1α expression. Methods Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 120 min. Rats were treated with different doses of orexin-A or vehicle before the ischemia and at the onset of reperfusion. To investigate the action of HIF-1α in the neuroprotective effects of orexin-A, the HIF-1α inhibitor YC-1 was used alone or combined with orexin-A. Neurologic deficit scores and infarct volume were assessed. Brains were harvested for immunohistochemical staining and western blot analysis. Results Orexin-A significantly ameliorated neurologic deficit scores and reduced infarct volume after cerebral ischemia reperfusion. Administration of 30 μg/kg orexin-A showed optimal neuroprotective effects. This effect was still present 7 days after reperfusion. Furthermore, orexin-A decreased the number of apoptotic cells and significantly enhanced HIF-1α expression after cerebral ischemia reperfusion. Moreover, the facilitation of HIF-1α expression was accompanied with inhibition of von Hippel-Lindau expression. Administration of HIF-1α inhibitor suppressed the increase of HIF-1α and reversed the neuroprotective effects of orexin-A. Conclusions Orexin-A has a neuroprotective effect against cerebral ischemia-reperfusion injury. These effects may be mediated through the HIF-1α pathway.

Objective: Adenosine pretreatment reduces injury caused by ischemia-reperfusion. To investigate the hypothesis that adenosine pretreatment would modulate injury induced by cardiopulmonary bypass (CPB) and myocardial ischemia/reperfusion, we conducted a randomized controlledtrial ontheeffects of adenosinepretreatment inchildrenundergoingsurgery to repaircongenitalheart defects.Methods:Children undergoing surgery to repair congenital heart defects were randomized to adenosine pretreatment or control treatment. Adenosine pretreatment was performed by infusing a total of 2.45 mg kg 1 of adenosine over 10 min. Serum troponin I was measured pre- and postoperatively. Multiple clinical parameters, including postoperative use of inotropic medicine and duration in the intensive care unit (ICU),wererecorded.Results:Atotalof82patientswereenrolledinthestudy.Therewere42controlpatientsand40patientsintheadenosine pretreatment group. The mean age and weight of the two groups were notsignificantly different, nor were cardiopulmonary bypass and crossclamp times. There were no deaths and severe complications in both groups. The adenosine pretreatment protocol caused significant hypotension but had no significant effect on heart rate. One patient had severe tachycardia shortly after the adenosine pretreatment protocol was completed, and adenosine infusion was continued until CPB was started. Postoperative levels of serum troponin I were greater in the controlpatientsthaninthe adenosinepretreatmentgroup,indicating thatthecontrolgroupsufferedgreatermyocardialinjury.Controlgroup patients required more postoperative inotropic agents than those in the adenosine pretreatment group at 0, 1, and 3 h, indicating that the adenosinepretreatment grouphadabettercardiac function.The adenosine pretreatment group also required significantly less time in the ICU than the control group (3.2 1.2 days vs 3.9 1.2 days, p = 0.013). Conclusions: This study demonstrates that adenosine pretreatment is protective of the myocardium during open-heart surgery in pediatric patients. # 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.