Integrated edge information and pathway topology for drug-disease associations.

Drug repurposing is a promising approach to find new therapeutic indications for approved drugs. Many computational approaches have been proposed to prioritize candidate anticancer drugs by gene or pathway level. However, these methods neglect the changes in gene interactions at the edge level. To address the limitation, we develop a computational drug repurposing method (iEdgePathDDA) based on edge information and pathway topology. First, we identify drug-induced and disease-related edges (the changes in gene interactions) within pathways by using the Pearson correlation coefficient. Next, we calculate the inhibition score between drug-induced edges and disease-related edges. Finally, we prioritize drug candidates according to the inhibition score on all disease-related edges. Case studies show that our approach successfully identifies new drug-disease pairs based on CTD database. Compared to the state-of-the-art approaches, the results demonstrate our method has the superior performance in terms of five metrics across colorectal, breast, and lung cancer datasets.

Effect of esketamine-based opioid-sparing anesthesia strategy on postoperative pain and recovery quality in patients undergoing total laparoscopic hysterectomy: A randomized controlled trail.

Objective: Opioid-sparing anesthesia reduces intraoperative use of opioids and postoperative adverse reactions. The current study investigated the effect of esketamine-based opioid-sparing anesthesia on total laparoscopic hysterectomy patients' recovery. Methods: Ninety patients undergoing total laparoscopic hysterectomy were randomly assigned to esketamine-based group (group K) or opioid-based group (group C). The allocation to groups was unknown to patients, surgeons, and postoperative medical staff. The inability to implement blinding for anesthesiologists was due to the distinct procedures followed by the various groups while administering drugs. The QoR-40 and VAS were used to measure recovery quality. Postoperative adverse events, perioperative opioid consumption, and intraoperative hemodynamics were secondary endpoints. Results: There was an absence of notable discrepancy in the baseline data observed between the two groups. The QoR-40 scores exhibited greater values in group K when compared to group C on the first day following the surgical procedure (160.91 ± 9.11 vs 151.47 ± 8.35, respectively; mean difference 9.44 [95 %CI: 5.78-13.11]; P < 0.01). Within 24 h of surgery, the VAS score of group K was lower at rest and during movement. (P < 0.05 for each). Group K had much lower rates of nausea and vomiting within 24 h of surgery. (P < 0.05 for each). Group K received significantly lower total doses of sufentanil and remifentanil than group C. (17.28 ± 2.59 vs 43.43 ± 3.52; 0.51 ± 0.15 vs 1.24 ± 0.24). The proportion of patients who used ephedrine in surgery was higher in group C than in group K (P < 0.05). Conclusions: Esketamine-based opioid-sparing anesthesia strategy is feasible and enhanced recuperation following surgery by decreasing adverse effects associated with opioids and pain scores compared to an opioid-based anesthetic regimen.

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

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

Intraspectrum Discrimination and Interspectrum Correlation Analysis Deep Network for Multispectral Face Recognition.

Multispectral images contain rich recognition information since the multispectral camera can reveal information that is not visible to the human eye or to the conventional RGB camera. Due to this characteristic of multispectral images, multispectral face recognition has attracted lots of research interest. Although some multispectral face recognition methods have been presented in the last decade, how to fully and effectively explore the intraspectrum discriminant information and the useful interspectrum correlation information in multispectral face images for recognition has not been well studied. To boost the performance of multispectral face recognition, we propose an intraspectrum discrimination and interspectrum correlation analysis deep network (IDICN) approach. Multiple spectra are divided into several spectrum-sets, with each containing a group of spectra within a small spectral range. The IDICN network contains a set of spectrum-set-specific deep convolutional neural networks attempting to extract spectrum-set-specific features, followed by a spectrum pooling layer, whose target is to select a group of spectra with favorable discriminative abilities adaptively. IDICN jointly learns the nonlinear representations of the selected spectra, such that the intraspectrum Fisher loss and the interspectrum discriminant correlation are minimized. Experiments on the well-known Hong Kong Polytechnic University, Carnegie Mellon University, and the University of Western Australia multispectral face datasets demonstrate the superior performance of the proposed approach over several state-of-the-art methods.

[Protective effect of shenfu injection pretreatment on brain of patients receiving aortic valve replacement undergoing cardiopulmonary bypass].

OBJECTIVE: To observe the protective effect of Shenfu Injection (SFI) pretreatment on brain of patients receiving aortic valve replacement (AVR) undergoing cardiopulmonary bypass (CPB). METHODS: Thirty AVR patients undergoing CPB were randomly assigned to 2 groups, the control group and the experimental group, 15 cases in each group. SFI at 1.5 mL/kg (dissolved in 250 mL 5% glucose solution) was intravenously dripped to those in the experimental group 5 days before operation, once daily for 5 successive days. SFI at 1.5 mL/kg (dissolved in 250 mL 5% glucose solution) was intravenously dripped to those 30 min before anesthesia induction. Equal dose of normal saline was intravenously dripped to those in the control group, and the other procedures were the same as those for patients in the experimental group. The venous blood sample (2 mL) was drawn from the right internal carotid vein immediately after induction of anesthesia (T1),10 min after CPB (T2), 30 min after GPB (T3), 2 h after CPB (T4), 24 h after CPB (T5), and 48 h after CPB (T6), thus detecting the plasma levels of S100beta and neuron specific enolase (NSE). And patients' cognitive function was assessed with mini-mental state examination (MMSE) scale on the day before operation, the 2nd and the 7th day after operation. RESULTS: There was no statistical difference in the levels of S1001 and NSE between the two groups at T1 (P > 0.05). There was statistical difference in the levels of S100beta and NSE between the two groups at T2, T3, T4, T5, T6, when compared with those at T1 (P <0.05). Besides, the levels of S100beta and NSE at T2, T3, T4, T5, T6 were lower in the experimental group than in the control group, showing statistical difference (P <0.05). The MMSE scores decreased on the 2nd day after operation in the two groups, showing statistical difference when compared with those on the day before operation (P <0.05). It was lowered more obviously in the control group. There was no statistical difference in the MMSE score between the 7th day post-operation and the day before operation (P >0.05). CONCLUSION: SFI pretreatment had protective effect on brain in AVR patients undergoing CPB.

Dual isoflurane-induced preconditioning improves neuroprotection in rat brain in vitro and the role of extracellular signal--regulated protein kinase.

OBJECTIVE: To test the ability of isoflurane-induced preconditioning against oxygen and glucose deprivation (OGD) injury in vitro. METHODS: Rat hippocampal slices were exposed to 1 volume percentage (vol%), 2vol% or 3vol% isoflurane respectively for 20 minutes under normoxic conditions (95% O2/5% CO2) once or twice (12 slices in each group) before OGD, with 15-minute washout after each exposure. During OGD experiments, hippocampus slices were bathed with artificial cerebrospinal fluid (ACSF) lacking glucose and perfused with 95% N2 and 5% CO2 for 14 minutes, followed by a 30-minute reperfusion in normal ACSF. The CA1 population spike (PS) was measured and used to quantify the degree of neuronal function recovery after OGD. To assess the role of mitogen-activated protein kinases (MAPKs) in isoflurane preconditioning, U0126, an inhibitor of extracellular signal-regulated protein kinase (ERK1/2), and SB203580, an inhibitor of p38 MAPK, were used before two periods of 3vol% isoflurane exposure. RESULTS: The degree of neuronal function recovery of hippocampal slices exposed to 1vol%, 2vol%, or 3vol% isoflurane once was 41.88%±9.23%, 55.05% ± 11.02%, or 63.18% ± 10.82% respectively. Moreover, neuronal function recovery of hippocampal slices exposed to 1vol%, 2vol%, or 3vol% isoflurane twice was 53.75% ± 12.04%, 63.50% ± 11.06%, or 76.25% ± 12.25%, respectively. Isoflurane preconditioning increased the neuronal function recovery in a dose-dependent manner. U0126 blocked the preconditioning induced by dual exposure to 3vol% isoflurane (6.13% ± 1.56%, P < 0.01) and ERK1/2 activities. CONCLUSIONS: Isoflurane is capable of inducing preconditioning in hippocampal slices in vitro in a dose-dependent manner, and dual exposure to isoflurane with a lower concentration is more effective in triggering preconditioning than a single exposure. Isoflurane-induced neuroprotection might be involved with ERK1/2 activities.

Duplicate preconditioning with sevoflurane in vitro improves neuroprotection in rat brain via activating the extracellular signal-regulated protein kinase.

OBJECTIVE: Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia-reperfusion (IR) injury, but the underlying mechanisms have not been fully elucidated. Besides, different protocols would usually lead to different results. The objective of this study was to determine whether dual exposure to sevoflurane improves the effect of anesthetic preconditioning against oxygen and glucose deprivation (OGD) injury in vitro. METHODS: Rat hippocampal slices under normoxic conditions (95% O2/5% CO2) were pre-exposed to sevoflurane 1, 2 and 3 minimum alveolar concentration (MAC) for 30 min, once or twice, with 15-min washout after each exposure. The slices were then subjected to 13-min OGD treatment (95% N2/5% CO2, glucose-free), followed by 30-min reoxygenation. The population spikes (PSs) were recorded in the CA1 region of rat hippocampus. The percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment was calculated, since it could indicate the recovery degree of neuronal function. In addition, to assess the role of mitogen-activated protein kinases (MAPKs) in preconditioning, U0126, an inhibitor of extracellular signal-regulated protein kinase (MEK-ERK1/2, ERK1/2 MAPK), and SB203580, an inhibitor of p38 MAPK, were separately added 10 min before sevoflurane exposure. RESULTS: Preconditioning once with sevoflurane 1, 2, and 3 MAC increased the percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment, from (15.13+/-3.79)% (control) to (31.88+/-5.36)%, (44.00+/-5.01)%, and (49.50+/-6.25)%, respectively, and twice preconditioning with sevoflurane 1, 2, and 3 MAC increased the percentage to (38.53+/-4.36)%, (50.74+/-7.05)% and (55.86+/-6.23)%, respectively. The effect of duplicate preconditioning with sevoflurane 3 MAC was blocked by U0126 [(16.23+/-4.62)%]. CONCLUSION: Sevoflurane preconditioning can induce neuroprotection against OGD injury in vitro, and preconditioning twice enhances this effect. Besides, the activation of extracellular signal-regulated protein kinase (MEK-ERK1/2, ERK1/2 MAPK) may be involved in this process.