Objective:To establish an acute kidney injury (AKI) prediction model in patients after cardiac surgery by extreme gradient boosting (XGBoost) machine learning model, and to explore the risk and protective factors for AKI in patients after cardiac surgery.Methods:All patients who underwent cardiac surgery in Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ) database were enrolled, and they were divided into AKI group and non-AKI group according to whether AKI developed within 14 days after cardiac surgery. Their clinical characteristics were compared. Based on five-fold cross-validation, XGBoost and Logistic regression were used to establish the prediction model of AKI after cardiac surgery. And the area under the receiver operator characteristic curve (AUC) of the models was compared. The output model of XGBoost was interpreted by Shapley additive explanations (SHAP).Results:A total of 6 912 patients were included, of which 5 681 (82.2%) developed AKI within 14 days after the operation, and 1 231 (17.8%) did not. Compared with the non-AKI group, the main characteristics of AKI group included older age [years: 68.0 (59.0, 76.0) vs. 62.0 (52.0, 71.0)], higher incidence of emergency admission and complicated with obesity and diabetes (52.4% vs. 47.8%, 9.0% vs. 4.0%, 32.0% vs. 22.2%), lower respiratory rate [RR; bpm: times/min: 17.0 (14.0, 20.0) vs. 19.0 (15.0, 22.0)], lower heart rate [HR; bpm: 80.0 (67.0, 89.0) vs. 82.0 (71.5, 93.0)], higher blood pressure [mmHg (1 mmHg ≈ 0.133 kPa): 80.0 (70.7, 90.0) vs. 78.0 (70.0, 88.0)], higher hemoglobin (Hb), blood glucose, blood K + level and serum creatinine [SCr; Hb (g/L): 122.0 (109.0, 136.0) vs. 120.0 (106.0, 135.0), blood glucose (mmol/L): 7.3 (6.1, 8.9) vs. 6.8 (5.7, 8.5), blood K + level (mmol/L): 4.2 (3.9, 4.7) vs. 4.2 (3.8, 4.6), SCr (μmol/L): 88.4 (70.7, 106.1) vs. 79.6 (70.7, 97.2)], lower albumin (ALB) and triacylglycerol [TG; ALB (g/L): 38.0 (35.0, 41.0) vs. 39.0 (37.0, 42.0), TG (mmol/L): 1.4 (1.0, 2.0) vs. 1.5 (1.0, 2.2)] as well as higher incidence of multiple organ dysfunction syndrome (MODS) and sepsis (30.6% vs. 16.2%, 3.3% vs. 1.9%), with significant differences (all P < 0.05). In the output model of Logistic regression, important predictors were lactic acid [Lac; odds ratio ( OR) = 1.062, 95% confidence interval (95% CI) was 1.030-1.100, P = 0.005], obesity ( OR = 2.234, 95% CI was 1.900-2.640, P < 0.001), male ( OR = 0.858, 95% CI was 0.794-0.928, P = 0.049), diabetes ( OR = 1.820, 95% CI was 1.680-1.980, P < 0.001) and emergency admission ( OR = 1.278, 95% CI was 1.190-1.380, P < 0.001). Receiver operator characteristic curve (ROC curve) analysis showed that the AUC of the Logistic regression model for predicting AKI after cardiac surgery was 0.62 (95% CI was 0.61-0.67). After optimizing the XGBoost model parameters by grid search combined with five-fold cross-validation, the model was trained well with no overfitting or overfitting. ROC analysis showed that the AUC of XGBoost model for predicting AKI after cardiac surgery was 0.77 (95% CI was 0.75-0.80), which was significantly higher than that of Logistic regression model ( P < 0.01). After SHAP treatment, in the output model of XGBoost, age and ALB were the most important predictors of the final outcome, where age was the risk factor (average |SHAP value| was 0.434), and ALB was the protective factor (average |SHAP value| was 0.221). Conclusions:Age is an important risk factor for AKI after cardiac surgery, and ALB is a protective factor. The performance of machine learning in predicting cardiac and vascular surgery-associated AKI is better than the traditional Logistic regression. XGBoost can analyze the more complex relationship between variables and outcomes, and can predict the risk of postoperative AKI more accurately and individually.

Objective:To observe the activation of microglia and the expression of inflammatory factors in hippocampus of mice with depression-like behavior after mother-infant separation （MS） combined with lipopolysaccharide （LPS） stress， and to explore the possible anti-depression mechanisms of Wenyang （WY）， Jieyu （JY）， and Wenyang Jieyu （WYJY） prescriptions from the perspective of warming Yang and relieving depression. Method:Seventy offspring mice were randomly divided into a normal group （n=10）， a LPS stress group （n=10）， and a modeling group （n=50）. After undergoing 8 h·d^-1 mother-infant separation during postnatal day 5 （PD₅）–PD₁₄， mice in the modeling group were further divided into the MS + LPS group， WY group， JY group， WYJY group， and fluoxetine （FLU） group， with 10 in each group. The birth date of the offspring mice was recorded as PD₀. The mice in the normal， LPS， and MS + LPS groups were fed a normal diet during PD₂₁–PD₉₀， while those in the other groups were treated with the mixtures of corresponding drugs and feed， followed by seven-day intraperitoneal injection of LPS since PD₉₁ for inducing depression. The depression-like behavior of mice in each group was detected in the open-field， O-maze， and social interaction tests. The protein expression of microglia-specific ionized calcium-binding adaptor molecule 1 （Iba-1） in the hippocampus was assayed by immunohistochemistry， and the mRNA expression of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， Iba-1， and glucocorticoid receptor （GR） by real-time fluorescence quantitative PCR （Real-time PCR）. Result:Compared with the normal group， the LPS group exhibited significantly reduced residence time at the central area within 5 min （P<0.01） and shortened total exercise distance （P<0.01）. In the MS + LPS group， the open-arm activity time and the total activity distance decreased significantly （P<0.01， P<0.05）， whereas the training， discrimination and exploration time increased significantly （P<0.01）. The expression of Iba-1 in hippocampal CA1 region of mice in the LPS and MS + LPS groups was remarkably elevated （P<0.01）. Compared with the LPS group， the MS + LPS group displayed significantly prolonged distance of 5-min exercise （P<0.05）， increased training， discrimination and exploration time （P<0.05， P<0.01）， and up-regulated Iba-1 expression in hippocampal CA1 area （P<0.01）. As revealed by comparison with the MS + LPS group， both the total 5-min exercise distance （P<0.01） and the training and discrimination time （P<0.01， P<0.05） of mice in each administration group was significantly shortened. The discrimination and exploration time of mice in the JY， WYJY， and FLU groups was significantly reduced （P<0.01）， and the expression of Iba-1 in hippocampal CA1 region of mice in each administration group was significantly down-regulated （P<0.01）. Conclusion:The warming Yang and relieving depression method helps to inhibit the occurrence and development of depression due to its efficacy in activating microglia in hippocampus of depression mice and lowering the expression of IL-1β， IL-6， and TNF-α.

Objective:To observe the activation of microglia in hippocampus of depressed and anxious mice induced by maternal separation with acute restraint stress and the expression of interleukin-1β（IL-1β），interleukin-6（IL-6），tumor necrosis factor-α（TNF-α）， investigating the mechanism of Wenyang Jieyu prescription in treating anxiety and depression. Method:Eighty four male C57BL offspring were randomly divided into control group， acute restraint stress group and model group on postnatal day 0（PD0）. Maternal separation combined with acute restraint stress was used to prepare anxious and depressed model mice， dividing the model mice into model group， Wenyang， Jieyu， Wenyang Jieyu and fluoxetine group according to random number table method. During the period of PD21-PD90， the control， acute restraint stress and model mice were fed with normal diet， with the other groups fed with corresponding medicine mixed diet. The Wenyang， Jieyu and Wenyang Jieyu groups were given 5.85， 12.03 and 16.71 g·kg^-1·d^-1 respectively. The fluoxetine group was given 2.60 mg·kg^-1·d^-1. Open field， zero maze test and social interaction tests were used to evaluate the anxiety and depression of model mice. The expression of Iba-1 in hippocampal microglia was detected by immunohistochemistry（IHC）. The mRNA expression of IL-1β， IL-6， TNF-α， Iba-1 and glucocorticoid receptor（GR）were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the control group， total movement distance and time spent in central zone in 5 min of the model mice significantly decreased（P<0.01）， time spent in opened arm and total movement distance decreased significantly（P<0.05，P<0.01）， investigation time during testing and training increased significantly（P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly increased（P<0.01）， the expression levels of GR mRNA significantly decreased（P<0.01）. The result of IHC staining showed that microglia were over activated. Compared with the model group， total movement distance and time spent in central zone in 5 min of mice in the Wenyang Jieyu and fluoxetine group significantly increased（P<0.05，P<0.01）.Time spent in opened arm significantly increased（P<0.01）. Investigation time during testing and training significantly decreased（P<0.05，P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly decreased（P<0.05，P<0.01）. The expression of GR mRNA increased significantly（P<0.05，P<0.01）. IHC staining showed the microglia recovered. Time spent in opened arm of mice in the Wenyang group and Jieyu group significantly increased （P<0.01）， time spent investigating during testing decreased significantly （P<0.05）， the expression levels of Iba-1 protein and mRNA，IL-6 mRNA significantly decreased （P<0.05，P<0.01）. The expression of GR mRNA of mice in the Wenyang group significantly increased （P<0.05）， the expression of TNF-α mRNA significantly decreased （P<0.05）. Total movement distance of mice in the Jieyu group increased significantly （P<0.01）， time spent investigating during training decreased significantly （P<0.05），the expression level of IL-1β mRNA significantly decreased （P<0.05）. IHC staining showed that microglia recovered partly in both groups. Conclusion:The comprehensive curative effect and pharmacological action of Wenyang Jieyu prescription were better than Wenyang prescription and Jieyu prescription. Wenyang Jieyu prescription can treat anxiety and depression in maternal separation and acute restraint stress mice， its possible mechanism may be related to the decreased activation of microglia， down-regulation of IL-1β，IL-6，TNF-α expression and up-regulation of GR expression.

Radiation-induced bystander effect (RIBE) refers to that irradiated cells release signaling factors and induce responses in nonirradiated cells.In other words, it is the communication between irradiated and nonirradiated cells by intracellular signals. RIBE could influence the efficacy of tumor radiotherapy, but also has potential risk to the normal tissues outside of radiation field. Studies have found that ionizing radiation can induce the alteration of miRNA expression not only in the irradiated cells but also in adjacent nonirradiated tissues, and miRNAs may play an important role in the regulation of signaling pathways between irradiated and nonirradiated bystander cells. This article reviewed the roles of miRNAs in RIBE.

Objective To systematically evaluate the effect of intranasal dexmedetomidine on agita-tion during emergence from general anesthesia with sevoflurane in pediatric patients. Methods Pubmed, Embase, The Cochrane Library, China National Knowledge Infrastructure, VIP, Wan-Fang databases were searched for randomized controlled trials involving the effect of intranasal dexmedetomidine on agitation during emergence from general anesthesia with sevoflurane in pediatric patients from the start of their data-base until June 2017, and the reference lists of all included studies were checked manually. Data were ex-tracted independently by two reviewers, and primary evaluation indexes included the incidence of emergence agitation and sedation score. Secondary evaluation indexes included emergence time, extubation time, du-ration of post-anesthesia care unit stay, postoperative consumption of analgesics, incidence of adverse reac-tions ( such as bradycardia, nausea and vomiting, pruritus, laryngeal spasm) during recovery from anes-thesia. The quality of methodology of included studies was assessed. Meta-analysis was conducted with Rev-Man 5. 3 software. Results Eight randomized controlled trials involving 520 pediatric patients were includ-ed in this meta-analysis. Compared with placebo group, the incidence of emergence agitation was signifi-cantly decreased, sedation score was increased, extubation time was prolonged ( P<0. 05) , no significant change was found in the duration of post-anesthesia care unit stay or incidence of postoperative nausea and vomiting in intranasal dexmedetomidine group ( P>0. 05) . The emergence time was prolonged in intranasal 0. 3-1. 0 μg∕kg dexmedetomidine group ( P<0. 05 ) , and no significant change was found in emergence time in intranasal dexmedetomidine 1. 0-2. 0μg∕kg group ( P>0. 05) . Conclusion Intranasal dexmedeto-midine can decrease the occurrence of agitation during emergence from general anesthesia with sevoflurane and raise the quality of emergence in pediatric patients.

OBJECTIVETo explore the anti-myeloma effect of suberoylanilide hydroxamic acid (SAHA) and on mouse myeloma cell line SP2/0 in vitro and in vivo and its mechanism.

METHODSThe inhibitory effect of SAHA on SP2/0 cells was measured by CCK-8 assay,and the apoptosis and cell cycle were analyzed by flow cytometry FACS. The protein expression of Caspase-3 and p53 of SP2/0 cells treated with SAHA were examined by Western blot. Annexin V/7-AAD double staining was performed to detect the apoptosis of SP2/0 induced by SAHA in vitro. SP2/0 cells (1×10) resuspended in 200 µl PBS were inoculated subcutaneously and intravenously into BALB/c mice, so as to establish aggressive or non-aggressive myeloma-bearing mouse models respectively. On day 3 after modeling, mice received SAHA or vehicle control treatment by intraperitoneal injection. The dose of SAHA was 60 mg/kg·d, 5 times a week for 3 weeks.

RESULTSIn SAHA-treated SP2/0 cells, the proliferation inhibition rate and apoptotic cells increased in a dose dependent manner. Also, SAHA significantly increased the ratio of cells in G phase and decreased in S phase. Molecular mechanisms of apoptosis and cell cycle arrest of SP2/0 induced by SAHA partly correlated with up-regulating the expression level of Caspase-3 and p53. In the non-aggressive myeloma-bearing mice, SP2/0 cells disappeared in peripheral blood after SAHA treatment. In the aggressive myeloma-bearing mice, inhibition of tumor growth and prolongation of the cell survival were observed after SAHA treatment.

CONCLUSIONSAHA inhibited SP2/0 cell proliferation, this effect associates with inducing apoptosis and cell cycle arrest, the mechanism of SAHA ralates partly with activating Caspase-3 and p53 pathway.

Animals ; Antineoplastic Agents ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Mice ; Mice, Inbred BALB C ; Multiple Myeloma

Objective To evaluate the prevalence of depressive symptoms and influencing factors among adolescents. Methods A total of 635 students aged 13 to 18 years were selected in March 2017 and were investigated with general information questionnaire, CES-D and CTQ-SF. Results 630 questionnaires are effective and the positive rate of depression was 29.84％(188/630) . The average score of CTQ was 32.15±2.98; 38.73％ of the students were disregarded and only 2.22％ of that were abused during their childhood. 40.00％ of the students had no CTQ, 1 kinds of CTQ accounted for 31.43％ , 2 kinds of CTQ accounted for 18.25％, and more than 3 CTQ accounted for 10.32％. Multivariate logistic regression analysis show that gender (OR=1.034, 95％ CI: 1.012-1.056) , parents' marital status (OR=1.124, 95％ CI: 1.087-1.162) , family atmosphere (OR=1.025, 95％ CI: 1.024-1.158) , CTQ cumulative number (ORCTQ=1=1.528, 95％ CI: 1.214-1.923; ORCTQ=2=3.067, 95％ CI: 1.325-7.102; ORCTQ≥3=10.361, 95％ CI: 3.059-35.093) were the risk factors for depression. Conclusion Gender, parents' marital status, family atmosphere and CTQ cumulative number were risk factors for depression in adolescents.

PURPOSETo investigate the effects of salvianolic acid B (SAB) on tumor necrosis factor a (TNF-α) induced alterations of cerebral microcirculation with a bone-abrading model.

METHODSThe influences of craniotomy model and bone-abrading model on cerebral microcirculation were compared. The bone-abrading method was used to detect the effects of intracerebroventricular application of 40 μg/kg·bw TNF-α on cerebral venular leakage of fluorescein isothiocyanate (FITC)- albulmin and the rolling and adhesion of leukocytes on venules with fluorescence tracer rhodamine 6G. The therapeutical effects of SAB on TNF-α induced microcirculatory alteration were observed, with continuous intravenous injection of 5 mg/kg·h SAB starting at 20 min before or 20 min after TNF-α administration, respectively. The expressions of CD11b/CD18 and CD62L in leukocytes were measured with flow cytometry. Immunohistochemical staining was also used to detect E-selectin and ICAM-1 expression in endothelial cells.

RESULTSCompared with craniotomy method, the bone-abrading method preserved a higher erythrocyte velocity in cerebral venules and more opening capillaries. TNF-α intervention only caused responses of vascular hyperpermeability and leukocyte rolling on venular walls, without leukocyte adhesion and other hemodynamic changes. Pre- or post-SAB treatment attenuated those responses and suppressed the enhanced expressions of CD11b/CD18 and CD62L in leukocytes and E-selectin and ICAM-1 in endothelial cells induced by TNF-α.

CONCLUSIONSThe pre- and post-applications of SAB during TNF-α stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling.

Animals ; Benzofurans ; pharmacology ; Blood Flow Velocity ; Cerebrovascular Circulation ; drug effects ; Craniotomy ; Disease Models, Animal ; E-Selectin ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Mice ; Mice, Inbred C57BL ; Microcirculation ; drug effects ; Random Allocation ; Reference Values ; Tumor Necrosis Factor-alpha ; administration & dosage

Objective To investigate the existence of pulmonary vascular remodeling after left pneumonectomy in rats and the role of hypoxia inducible factor-lα( HIF-1α) and vascular endothelial growth factor ( VEGF) in pulmonary vascular remodeling.Methods Twenty-four healthy male Sprague-Dawley rats were randomly divided into experimental and control groups, 12 in each group.The rat models of pulmonary vascular remodeling were created by open-chest left pneumonectomy.After 12 weeks of feeding, the mean pulmonary artery pressure ( mPAP) and partial pressure of arterial oxygen ( PaO2 ) of each rat were measured.The ultrastructure of small arteries in the lung specimens were examined by e-lectron microscopy.Muscularized degree of three kinds of small pulmonary vessels ( muscularized artery MA, partially mus-cularized artery PMA, and non-muscularized artery NMA) were observed by light microscopy, and the percentage of each kind of pulmonary arteries ( MA%, PMA%, NMA%) were calculated.Arterial external diameter, media thickness of ves-sel ( MTV) , total vascular area, media area of vessel ( MAV) , MTV%and MAV%were calculated as indicators of pul-monary vascular remodeling.The expressions of HIF-1αand VEGF in artery were detected by immunohistochemistry.Re-sults The values of mPAP, MA%, PMA%, MTV, MAV, MTV% and MAV% in the experimental group were signifi-cantly higher than those in the control group (P<0.01), but the value of PaO2 and NMA%were significantly lower than those in the control group (P<0.01).The IOD value of HIF-1αand VEGF expressed in the pulmonary arterial wall of the experimental group were 26.47 ±4.16 and 42.04 ±3.79, respectively, significantly higher than those in the control group (6.12 ±2.14 and 11.53 ±2.29, P<0.01).Linear correlation analysis showed that the expression of HIF-1αand VEGF was positively correlated with MTV% and MAV%, negatively correlated with PaO2 , and the HIF-1αexpression was posi-tively correlated with VEGF expression.Conclusions A rat model of pulmonary vascular remodeling can be successfully established by left pneumonectomy.Hypoxia is a key factor in the development of pulmonary vascular remodeling, HIF-1αand VEGF may play an important role in its pathogenesis.

Cardiac hypertrophy is a common phenomenon in heart disea-ses, ultimately lead to heart failure.Hepatocyte growth factor (HGF), which is a pleiotropic cytokine.It has been considered as a promising candidate for cardiovascular therapy for several years .This review focus on these molecular mechanisms and signaling pathways of HGF targeted in cardiovascular system , and summarizes current research about HGF on cardiac hypertrophy , analyses the potential contribution or adverse effect of HGF on cardiac hypertrophy turns out in different heart diseases.