AIM: To explore the influence of clonidine on inflammatory response in lung injury mice and its possible mechanism.METHODS: Clonidine solution was intravenously injected into the mice with lung injury induced by LPS.The left upper lobe of the lung was collected to detect lung wet/dry weight ratio (W/D) and total lung water content (TLW).The concentrations of IL-6, IL-1β and TNF-α were measured by ELISA.The expression of α7 nicotinic acetylcholine receptor (α7nAChR) and high-mobility group box protein 1 (HMGB1) at mRNA and protein levels was determined by RT-PCR and Western blot.After importing α7nAChR siRNA lentiviral vector or injecting exogenous HMGB1 protein, the inflammatory cytokines were detected.RESULTS: Clonidine attenuated lung injury and inhibited inflammatory reaction.Clonidine promoted the activation of cholinergic anti-inflammatory pathway by promoting α7nAChR expression.Clonidine inhibited HMGB1 expression, which promoted the secretion of IL-6, IL-1β and TNF-α.HMGB1 was negatively regulated by α7nAChR.CONCLUSION: Clonidine functions as an anti-inflammatory reagent to the lung injury mice.The mechanism may be related to activating the cholinergic anti-inflammatory pathway and inhibiting the expression of HMGB1.

Objective To investigate the effect of resveratrol (RES)on sevoflurane-induced nerve cell injury and its mechanism.Methods Fetal hippocampal tissues were taken from SD pregnant rats and primary nerve cells were isolated and cultured,then the cells were randomly divided into four groups:group control (group C),normal primary nerve cells;group 3% sevoflurane (group S),cells treated with 3% sevoflurane gas;group 3% sevoflurane+RES (group SR),cells treated with RES for 6 h,and then treated with 3% sevoflurane gas;group RES (group R),cells treated with RES.Flow cytometry assay was used to detect the apoptosis of nerve cell;CCK-8 Kit was used to detect cell proliferation;Western blot was used to detect the expression level of Caspase-3,Bax,Bcl-2 and Bace-1;ELISA method was used to detect the protein level of amyloid precursor protein (APP)andβ-amyloid peptide (Aβ).Results Compared with the group C,cell apoptosis was increased (P <0.05),cell proliferation was decreased (P <0.05),the expression levels of Caspase-3 and Bax were up-regulated (P <0.05),the expression level of Bcl-2 was down-regulated (P <0.05), and the protein levels of Bace-1,APP and Aβwere significantly decreased by 3% sevoflurane treat-ment (P <0.05),which were all significantly reversed by RES treatment.Compared with group S, cell apoptosis was decreased (P <0.05),cell proliferation was increased (P <0.05),the expression levels of Caspase-3 and Bax were down-regulated (P <0.05),the expression level of Bcl-2 was up-regulated (P <0.05),and the protein levels of Bace-1,APP and Aβwere increased in group SR (P <0.05).Conclusion Resveratrol alleviated sevoflurane-induced nerve cell injury in vitro by reducing cell apoptosis and promoting cell proliferation,which may be related with the reduction of Aβexpression and the reduced Aβ-induced neurotoxicity.

ObjectiveTo discuss the feasibility of the method that can be used to induce the model of type 2 diabetic mellitus rat and explore the characteristic of the nephropathy.The rats were fed with the high sucrose,high fat and high energy feed for a long time and then it was injected with the low dose STZ.Methods30 SD rats were selected and then it was randomly divided them into 2 groups,the control group (10 rats) and the model group (20 rats).The model group was fed with the high calorie feed forl0 weeks to induce insulin resistance and then the rats were induced to type 2 diabetes mellitus by injection of streptozocin (30 mg/kg).The rats of the model group were continually fed with the high calorie feed for 2 months.Before the end of this study,the 24-hours microalbuminuria,serum creatinine and blood urea nitrogen were detected and the periodic acid Schiff staining on the kidney were also measured.ResultsAfter the rats of the model group were established,the levels of the bodyweight,the cholesterol,the triglyceride and the insulin were [ (468.7 ± 8.8 ) g,( 1.92 ± 0.27 ) mmol/L,( 1.32 ± 0.34) mmol/L,(38.81 ± 5.39 ) mU/L ] respectively,all of them were higher than the levels in the normal group,which were [ (436.9 ± 7.4) g,(1.16 ±0.17)mmol/L,(0.8 ±0.18)mmo1/L,(21.43 ±4.19)mU/L],respectively( t =9.755,8.077,4.437,8.902,P ＜ 0.01 ).After injection of STZ for 2 weeks,the levels of the blood glucose,the insulin and the insulin resistance of the diabetes mellitus rats were [ ( 19.31 ± 1.55 ) mmol/L,( 31.31 ± 8.60) mU/L,(26.55 ± 6.33) ] respectively,it was higher than levels inf the normal group,which was[ (5.45 ±0.69) mmol/L,( 19.97 ± 3.26) mU/L,(4.82 ± 0.84) ] ( t =26.383,3.951,10.719,P ＜ 0.01 ).Before the end of this study,the levels of the blood glucose,insulin resistance,24-hours microalbuminuria,serum creatinine,blood urea nitrogen of the diabetes mellitus rats were [ ( 19.27 ± 1.97 ) mmol/L,( 16.70 ±7.51 ),(72.49 ± 8.53 ) mg/24 h,( 74.76 ± 8.38 ) μmol/L,( 19.09 ± 4.21 ) mmol/L],it was higher than the levels in the normal group,which were [ (5.62 ±0.65) mmol/L,(5.45 ± 1、33),( 15.26 ±2.20) mg/24 h,(40.81 ± 1.97) μmol/L,(9.87 ±2.13) mmol/L,t =20.961,4.657,20.623,12.495,6.352,P ＜0.01 ].And the pathological changes of the diabetes mellitus rats kidney tissues were the most serious through themethod of periodic acid-Schiff's staining (PAS).ConclusionsThe model of type 2 diabetic mellitus rat was constructed through the way of feeding the SD rats with high sucrose,high fat and high energy feed for a long time and low dose STZ.The diabetic mellitus rats had the symptom of drinking more,eating more and diuresis,and the character of this model had high levels of albuminuria,serum creatinine,blood urea nitrogen.The incrassated glomerular mesangium,the crescent-shaped focus and the glomerulosclerosis were also observed through the PAS.

Objective To investigate the effects of modafinil,a new wake-promoting agent,on simulated flight performance during 48 h sleep deprivation(SD).Method Six male healthy young volunteers were exposed to two periods of 48 h continuous wakefulness during the crossover experiment.In one period,three 200 mg doses of modafinil were given and in the other,separated by two weeks,matching placebos were administered.The SD time started from 8:00 of the first day to 8:00 of the third day.Drug was given at 0:00,16:00 of the second day and 0:00 of the third day.Flight performance in J7-E flight simulator was tested at 21:00 of the first day and 1,3,5,7 h after each drug administration.Result The scores of simulated flight performance in the placebo group decreased with time during SD and became significant at 1:00～7:00 of the third day.Numbers of errors increased with time during SD,especially in the left ascending turn stage and the descending & landing stages.Compared with the placebo,flight performance was significantly increased after the third administration of modafinil.Numbers of errors during 48 h SD and at 1:00～7:00 of the third day in modafinil group was 19% and 40% lower than those in placebo group respectively.Conclusion Simulated flight performance during 48 h SD is significantly improved after repeated administration of modafinil,especially when the impacts of SD and the circadian trough are combined.

BACKGROUND:Dorsal digital block refers to the commonly used anesthesia for adults in smal or moderate hand injury surgeries, but in recent years, modified transthecal digital block technique is gradualy respected, which is favored with a rapid and good effect and fewer complications.
OBJECTIVE:To evaluate the clinical anesthetic outcomes of modified transthecal digital block and traditional dorsal digital block technique for the treatment of hand injury of adults in emergency by a prospective randomized controled study.
METHODS:Totaly 60 adult patients with hand injury were enroled and divided into two groups of modified transthecal digital block and traditional dorsal digital block randomly. Blocks were performed by one single surgeon. The operation time, local anesthetic dose, onset time of anesthesia, duration of anesthesia, success rate of anesthesia, visual analogue scale scores and complications were recorded.
RESULTS AND CONCLUSION:The anesthesia effects in the two groups were acceptable. There was no significant difference in the onset time of anesthesia, duration of anesthesia, success rate of anesthesia and complications between the two groups (P > 0.05). The operation time of anesthesia, local anesthetic dose, and visual analogue scale scores were significantly different between the two groups (P< 0.05). Modified transthecal digital block is more convenient and has less pain than the traditional root digital block, which is a safe and reliable anesthetic technique.

OBJECTIVETo explore the role of P38 signaling pathway in neonatal rat astrocyte swelling and the expression of aquaporin-4 (AQP4) after oxygen-glucose deprivation (OGD) and recovery (OGD/R).

METHODSPrimarily cultured neonatal rat astrocytes were subject to OGD for 5 h followed by oxygen-glucose recovery in the presence or absence of the P38 inhibitor SB203580 (10 µmol/L). The astrocytes were investigated at 0.5, 2, 8 and 24 h after oxygen-glucose recovery for morphological changes and cell injuries using lactate dehydrogenase (LDH) assay. The expressions of P38, P-P38, and AQP4 mRNAs and proteins in the astrocytes were detected using RT-PCR and Western blotting.

RESULTSOGD/R caused significantly enhanced expression of P-P38 protein, and this effect was blocked by SB203580. AQP4 mRNA and protein expression declined transiently at 0.5 h after OGD and increased gradually to reach the peak level at 8 h (P<0.05). Application of the SB203580 significantly lowered OGD-induced AQP4 mRNA and protein up-regulation (P<0.05). Astrocyte swelling occurred after OGD/R but was obviously lessened by SB203580. LDH release increased markedly after OGD/R, and was attenuated by treatment with SB203580 (P<0.01).

CONCLUSIONP38 signaling pathway participates in astrocyte swelling after OGD/R, and blocking this pathway can attenuate AQP4 up-regulation and ameliorate the cell swelling.

Animals ; Animals, Newborn ; Aquaporin 4 ; metabolism ; Astrocytes ; metabolism ; pathology ; Brain Edema ; metabolism ; pathology ; Cell Hypoxia ; Glucose ; pharmacology ; MAP Kinase Signaling System ; physiology ; Oxygen ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism

Objective TNF-α monoclonal antibody drugs are widely used to treat conditions such as rheumatic arthritis and ankylosing spondylitis. On the other hand, it is also a wide concern that the application of these drugs may increase the susceptibility of patients to infections such as tuberculosis and listeriosis. The aim of this study was to establish a mouse model of Listeria monocytogenes infection and to evaluate the effect of TNF-α monoclonal antibody on the host susceptibility to this infection. Methods Six SPF 14-week old female C57BL/6 mice and 12 SPF 14-week old female TNF-α humanized mice were injected with saline or adalimumab intravenously, and challenged with intraperitoneal injection of 104 CFU Listeria monocytogenes 24 h later. After one day or 4 days, the mice were sacrificed to examine the pathological lesions and the bacterial load in the spleen and liver. Results Four days after infection, the area of microabscess in the liver tissues was significantly increased in the adalimumab-treated group. The bacterial load in the spleen and liver tissues of the adalimumab-treated group was significantly higher than that of the C57BL/6 mouse control group and TNF-α humanized mouse control group (P ＜ 0. 05). However, the distribution of macrophages in the liver tissues and B cells in the spleen tissues were similar among groups. Conclusions TNF-α plays an important role in the host immune responses to Listeria monocytogenes infection. After the intervention with TNF-α monoclonal antibody, the progress of host disease is significantly exacerbated.

OBJECTIVETo explore the role of p38 signal pathway in regulating matrix metalloproteinase-9 (MMP-9) expression and brain edema formation in a rat model of traumatic brain injury (TBI).

METHODSA total of 130 adult male Sprague Dawley rats were randomly divided into 4 groups, namely the normal group (n=10), sham-operated group (n=40), TBI (induced by Feeney free falling methods) group (n=40), and SB group with intraperitoneal SB203580 treatment (10 µmol/L) 15 min before TBI (n=40). The rats were sacrificed 2 h and 2 days after TBI. The expressions of p38, p-p38, and MMP-9 mRNA and protein were detected by RT-PCR and Western blotting. The blood brain barrier permeability was detected by Evans Blue (EB) test, and the brain water content (BWC) was determined using a gravimetric technique.

RESULTSThe expression of p-p38 protein increased markedly 2 h after TBI (P<0.05), and was suppressed by SB203580 treatment (P<0.05). MMP-9 mRNA and protein showed no obvious increase at 2 h after TBI, but significantly increased at 2 days as compared with those in the sham-operated group (P<0.05). MMP-9 mRNA and protein were much lower in SB group than in TBI group 2 days after TBI (P<0.05). The blood brain barrier permeability significantly increased 2 h after TBI (P<0.05) and kept increasing until 2 days (P<0.05), but was reduced significantly by SB203580 (P<0.05). BWC increased obviously 2 days after TBI (P<0.05) and was lessened by SB203580 (P<0.05).

CONCLUSIONBlocking p38 signal pathway can attenuate MMP-9 upregulation and brain edema after TBI, suggesting the important role of p38 in regulating MMP-9 expression to affect traumatic brain edema.

Animals ; Brain Edema ; pathology ; Brain Injuries ; metabolism ; Enzyme Inhibitors ; pharmacology ; Imidazoles ; pharmacology ; MAP Kinase Signaling System ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley

Objective To examine the predictive value of fetal umbilical artery Doppler in preterm birth in pregnant women with systemic lupus erythematosus(SLE).Methods The clinical data from 160 live births of SLE patients were analyzed retrospectively.Results The mean age of SLE patients at pregnancy was(29.7 ± 3.7) years(20 ~ 37 years). Totally,56 patients(32.5%)were preterm births and 76(47.5%)were full-term births without any other adverse pregnancy outcomes. The rate of preterm birth before 34 weeks was 26.9% and that was 73.1% for those preterm deliveries after 34 weeks. Iatrogenic preterm birth was the most common cause of preterm birth(32 cases),followed by spontaneous preterm birth(12 cases)and preterm premature rupture of membranes (10 cases).The pulsatility index(PI),resistance index(RI)as well as S/D value of SLE patients with pre-term delivery was higher than those of patients with full-term delivery(P<0.05).The area below the ROC curve for PI, RI and S/D was 0.6(95% CI 0.5~0.7),0.7(95% CI 0.6~0.8)and 0.6(95% CI 0.5~0.7),respectively.PI with cut-off value of 1.0 indicated the highest risk of preterm birth,with sensitivities of 34.6% and 84.2.The optimal cut-off value for RI and S/D was 0.7 and 2.8 respectivly,at which sensitivity and specificity had the best combination. Conclusions Pregnancies in lupus still have an increased risk of preterm birth. Umbilical artery Doppler was a useful monitoring tool for preterm birth in lupus pregnancies.