Objective To estimate and compare the efficacy and safety of midazolam, propofol and dexmedetomidine combined with propofol in sedation for mechanically ventilated patients. Methods Seventy-six patients with mechanical ventilation time >24h in ICU of Navy General Hospital of PLA from Mar. 2012 to Sep. 2014 were randomly divided into midazolam group (n=23), propofol group (n=27) and dexmedetomidine combined with propofol group (n=26), and they were given corresponding drugs for sedation. The proportions in each group which reached the target score of Richmond agitation-sedation scale (RASS) and the nonverbal pain assessment scale (Critical-Care Pain Observation Tool, CPOT) were accounted and recorded, and the positive rate of delirium was assessed with the confusion assessment method in the intensive care unit (CAM-ICU). The mechanical ventilation time and the effectiveness of sedation among the 3 groups were compared, the frequency of adverse cardiovascular events was recorded, and the frequency of controlled ventilation, daily mean arterial pressure as well as the heart rate range were analyzed. Results The proportion of reaching the target score of RASS was higher in dexmedetomidine combined with propofol group (86.54%) than that in midazolam group (69.32%, P<0.05), but there was no significant difference when compared with that in propofol group (79.37%, P>0.05). The proportion of reaching the target score of CPOT was higher in dexmedetomidine combined with propofol group (63.1%) than in midazolam group (51.2%) and propofol group (49.5%, P<0.05), but no significant difference was found between the latter two groups (P>0.05). The positive rate of delirium and the proportion of controlled ventilation were lower, and the time of mechanical ventilation is shorter in dexmedetomidine combined with propofol group than in the other two groups (P<0.05). No significant difference in the proportion of adverse cardiovascular events, mean arterial pressure and heart rate range was found among the three groups (P>0.05). Conclusion The efficacy and safety of dexmedetomidine combined with propofol is higher than the individual use of midazolam or propofol in producing sedation for mechanically ventilated patients.

Aim To explore the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in high fat-induced oxidative stress injury in human umbilical vein endothelial cells (HUVECs).Methods HUVECs were exposed to different concentrations of palmitic acid(0.1,0.2,0.4,0.8 mmol · L-1) for 24 h and different time points of 0.4 mmol · L-1 palmitic acid(0,12,24,48 h).Cell viability was measured by Cell Counting Kit 8,and the protein expression of NADPH oxidase subunits such as p22phox,p47phox,p67phox and gp91phox were determined by Western blot.The expression of reactive oxygen species (ROS) in HUVECs was detected by immunofluorescence.Results Cell proliferation rate of HUVECs stimulated by 0.4 mmol · L-1 palmitic acid for 24 h and 48 h was significantly reduced.In the next experiment,model group was accordingly set as HUVECs stimulated by 0.4 mmol · L-1 palmitic acid for 24 h.The expression of NADPH oxidase subunits such as p22phox,p47phox,p67phox and gp91phox significantly increased at 24 h and 48 h after 0.4 mmol· L-1 palmitic acid stimulation (P ＜ 0.05),and the difference.between the 24 h group and the 48 h group was not significant (P ＞ 0.05).The expression of ROS in HUVECs significantly increased at 24 h and 48 h after O.4 mmol · L-1 palmitic acid stimulation (P ＜ 0.05),and the difference between 24 h group and 48 h group was not significant (P ＜ 0.05).Compared with the model group (0.4 mmol · L-1 palmitic acid stimulation for 24 h),the NADPH oxidase inhibitor diphenyliodonium (DPI,10 μmol · L-1) pretreatment could significantly decrease the expression of ROS in vascular endothelial cells (P ＜ 0.05).Conclusion Activated NADPH oxidase might play an important role in treatment of high fat-induced oxidative stress injury in vascular endothelial cells.

Aim To explore the role of endoplasmic reticulum stress(ERS)signaling pathway in high fat-induced cell apoptosis in human umbilical vein endo-thelial cells(HUVECs). Methods HUVECs were ex-posed to different concentrations of palmitic acid(0. 1, 0. 2,0. 4,0. 8 mmol·L - 1 )for 24 h and different time points of 0. 4 mmol·L - 1 palmitic acid(0,12, 24,48 h). Cell viability was measured by cell count-ing kit(CCK-8),and the protein expressions of ERS signaling pathway protein such as GRP78,CHOP, PERK,IRE1,ATF6 were determined by Western blot. The level of intracellular apoptosis was detected by immunofluorescence. Results HUVECs exposed to palmitic acid at 0. 4 mmol·L - 1 for 24 h showed a de-crease in their viability and an increase in the expres-sion of ERS signaling pathway proteins (GRP78, CHOP,PERK,IRE1,ATF6)(P < 0. 05);cell ap-optotic levels significantly increased(P < 0. 05). The intracellular apoptosis levels in the vascular endothelial cells of ERS signaling pathway inhibitor 4-phenylbutyr-ic acid (4-PBA,10 mmol · L - 1 )were significantly lower than those of the PA group(P < 0. 05). Conclu-sion Activated ERS signaling pathway might play an important role in the treatment of high fat-induced cell apoptosis in vascular endothelial cells.

Objective To investigate the effects of Panax Notoginseng saponins (PNS) on protein expression of Klotho in rats with renal ischemia reperfusion injury; To discuss its protective mechanism for model rats. Methods Experimental rats were randomly divided into sham-operation group, model group, positive medicine group, PNS high-, medium- and low-dosage groups. Each administration group was given relevant medicine for gavage, once a day. Renal ischemia reperfusion injury model was established. Rats were sacrificed by taking blood from abdominal aorta after 4 hours of modeling. Serum levels of blood urea nitrogen (BUN), creatinine (SCr), malondialdehyde (MDA) content in kidney tissue, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity were measured. HE staining was used to observe the morphological changes of renal tissue. The protein expressions of Klotho and NF-κB p65 were measured by immunohistochemical method. Results Compared with the sham-operation group, the levels of BUN and SCr in the model group increased significantly (P<0.05); protein expression of Klotho in renal tissue decreased and the protein expression of NF-κB p65 increased (P<0.05). Compared with the model group, the expression of Klotho increased but protein expression of NF-κB p65 decreased in each administration group (P<0.05); Compared with the positive medicine group, the expression of Klotho in PNS high-dosage group increased but protein expression of NF-κB p65 decreased (P<0.05). The protein expression of NF-κB p65 was negatively related to protein expression of Klotho (r=-0.895, P<0.05). Conclusion PNS can inhibit oxidative stress and anti-inflammatory effects through upregulating protein expression of Klotho, and reduce the protein expression of NF-κB p65, and thus exerts renal protective effects.

Objective:To investigate the effect of TLK2 expression regulated by miR-21 on proliferation and apoptosis of acute myeloid leukemia cells.Methods:Seventy patients with AML admitted to our hospital from January 2019 to July 2022 were selected,while 30 patients with iron deficiency anemia were selected as the control group.Bone marrow mononuclear cells(BMMNCs)of the patients were obtained using Ficoll density gradient centrifugation.RT-qPCR was used to determine the expression levels of miR-21 and TLK2 mRNA in BMMNCs.Mimics-miR-21,mimics-NC,inhibitor-miR-21,inhibitor-NC and NC were transfected into HL-60 cells using liposome-mediated transfection technology.CCK-8 method was used to determine the activity of transfected HL-60 cells after treatment with cytarabine.The apoptosis rate of HL-60 transfected cells was determined by TUNEL method.The expression of TLK2 mRNA in HL-60 cells transfected with inhibitor-miR-21 was determined by RT-qPCR.Results:The relative expression levels of miR-21 and TLK2 mRNA in BMMNCs of AML patients were significantly higher than those of controls(both P＜0.05).After HL-60 cells were treated with cytarabine,both the cell activity of inhibitor-miR-21 group and mimics-miR-21 group decreased significantly with the increase of cytarabine concentration(both P＜0.05).However,at each concentration point of cytarabine,the cell activity of inhibitor-miR-21 group was lower than that of control group(P＜0.05),while mimics-miR-21 group was higher than control group(P＜0.05).After HL-60 cells were treated with cytarabine,the apoptosis rate of inhibitor-miR-21 group was significantly increased(P＜0.05),while that of mimics-miR-21 group was significantly decreased(P＜0.05).After HL-60 cells were treated with inhibitor-miR-21,the relative expression of TLK2 mRNA decreased significantly(P＜0.05).Conclusion:miR-21 is highly expressed in AML patients,which may promote the apoptosis of AML cells by inhibiting the expression of TLK2.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

OBJECTIVESTo investigate possible abnormalities of the sperm neck in eight infertile painters observed by transmission electron microscope.

METHODSSpermatozoa from 8 infertile painters (21-32 years old) were observed by transmission electron microscope.

RESULTSThe abnormalities of the connecting piece could be divided into 6 types, among which the anomaly of the connecting piece concomitant with a true nuclemalamic condition was the most serious.

CONCLUSIONSThe abnormalities may be related to expression obstacles of nuclear genome and mitochondrial genome, and to anomalous cellular signal transduction during spermiogenesis as well.

Adult ; Humans ; Infertility, Male ; pathology ; Male ; Microscopy, Electron, Transmission ; Occupational Exposure ; Paint ; adverse effects ; Spermatozoa ; ultrastructure

OBJECTIVETo explore the eukaryotic expression of arresten in CHO cells and to investigate its basic biological activities.

METHODSCHO cells were divided into three groups: transfected pSecTag-arresten group, transfected pSecTag group and control group without transfection. PSecTag-arresten was transfected into CHO cells by Lipofectamine 2000 method. The arresten mRNA in CHO cells was assayed by RT-PCR. The protein expression of arresten gene was examined by Western-Blot. The cells expressing arresten were screened out by Zeocin. The effect of arresten on huvec cell migration and anchoring to three-dimensional vascular structures was measured.

RESULTSThe result of RT-PCR and Western-blot showed that arresten gene has been successfully transfected into CHO cells and expressed in those cells. Arrssten inhibited huvec cell migration and anchoring to three-dimensional vascular structures.

CONCLUSIONCHO cells expressing arresten have been obtained successfully. Arresten can inhibit huvec cell migration and anchoring to three-dimensional vascular structures, indicating that it might be one of its anti-angiogenetic approaches.

Angiogenesis Inhibitors ; biosynthesis ; genetics ; pharmacology ; Animals ; Blotting, Western ; CHO Cells ; Cell Line ; Cell Movement ; drug effects ; Cells, Cultured ; Collagen Type IV ; biosynthesis ; genetics ; pharmacology ; Cricetinae ; Cricetulus ; Endothelial Cells ; cytology ; drug effects ; physiology ; Humans ; Neovascularization, Physiologic ; drug effects ; RNA, Messenger ; biosynthesis ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection

OBJECTIVETo investigate the protective effect of hepatocyte growth factor (HGF) on protein synthesis in rat cardiomyocytes exposed to gamma-ray irradiation.

METHODSPrimary cultured cardiomyocytes were irradiated with single-dose (20 Gy) gamma ray in the absence or presence of HGF (40 ng/ml) added in the cell culture 3 h before the exposure. Forty-eight hours after irradiation, the total cellular protein was measured and cell cycle analyzed by flow cytometry. The cardiomyoctes were also infected with AdGFP 48 h after irradiation and the fluorescence intensity of the green fluorescence protein (GFP) in the cells determined by flow cytometry 48 h after infection.

RESULTSThe protein synthesis was decreased significantly in the irradiated cardiomyocytes as compared with the control group (P<0.01), but was remedied significantly by incubation of the cells with HGF before the exposure (P<0.05). Flow cytometry revealed much lower mean fluorescence intensity (MFI) of GFP in irradiated cardiomycytes than in cells without the exposure (P<0.01); The MFI was higher in HGF-treated cardiomyocytes than in cells without HGF treatment following the exposure (P<0.01).

CONCLUSIONGamma ray irradiation inhibits protein synthesis in cardiomyocytes, and HGF may attenuate this effect of gamma ray exposure for cardiomyocyte protection.

Animals ; Animals, Newborn ; Cell Cycle ; drug effects ; radiation effects ; Cells, Cultured ; Flow Cytometry ; Gamma Rays ; Green Fluorescent Proteins ; genetics ; metabolism ; Hepatocyte Growth Factor ; pharmacology ; Microscopy, Fluorescence ; Myocytes, Cardiac ; cytology ; metabolism ; Protein Biosynthesis ; drug effects ; radiation effects ; Rats ; Rats, Wistar

BACKGROUNDVarious methods can be applied to build predictive models for the clinical data with binary outcome variable. This research aims to explore the process of constructing common predictive models, Logistic regression (LR), decision tree (DT) and multilayer perceptron (MLP), as well as focus on specific details when applying the methods mentioned above: what preconditions should be satisfied, how to set parameters of the model, how to screen variables and build accuracy models quickly and efficiently, and how to assess the generalization ability (that is, prediction performance) reliably by Monte Carlo method in the case of small sample size.

METHODSAll the 274 patients (include 137 type 2 diabetes mellitus with diabetic peripheral neuropathy and 137 type 2 diabetes mellitus without diabetic peripheral neuropathy) from the Metabolic Disease Hospital in Tianjin participated in the study. There were 30 variables such as sex, age, glycosylated hemoglobin, etc. On account of small sample size, the classification and regression tree (CART) with the chi-squared automatic interaction detector tree (CHAID) were combined by means of the 100 times 5-7 fold stratified cross-validation to build DT. The MLP was constructed by Schwarz Bayes Criterion to choose the number of hidden layers and hidden layer units, alone with levenberg-marquardt (L-M) optimization algorithm, weight decay and preliminary training method. Subsequently, LR was applied by the best subset method with the Akaike Information Criterion (AIC) to make the best used of information and avoid overfitting. Eventually, a 10 to 100 times 3-10 fold stratified cross-validation method was used to compare the generalization ability of DT, MLP and LR in view of the areas under the receiver operating characteristic (ROC) curves (AUC).

RESULTSThe AUC of DT, MLP and LR were 0.8863, 0.8536 and 0.8802, respectively. As the larger the AUC of a specific prediction model is, the higher diagnostic ability presents, MLP performed optimally, and then followed by LR and DT in terms of 10-100 times 2-10 fold stratified cross-validation in our study. Neural network model is a preferred option for the data. However, the best subset of multiple LR would be a better choice in view of efficiency and accuracy.

CONCLUSIONWhen dealing with data from small size sample, multiple independent variables and a dichotomous outcome variable, more strategies and statistical techniques (such as AIC criteria, L-M optimization algorithm, the best subset, etc.) should be considered to build a forecast model and some available methods (such as cross-validation, AUC, etc.) could be used for evaluation.

Case-Control Studies ; Decision Trees ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Neuropathies ; diagnosis ; etiology ; Humans ; Logistic Models