Objective To evaluate the effects of dexmedetomidine on the expression of spinal matrix metalloproteinase-9 (MMP-9) in a rat model of neuropathic pain (NP).Methods Eighty-one adult male SpragueDawley rats,weighing 190-230 g,were randomly divided into 3 groups (n =27 each) using a random number table:sham operation group (group S); group NP; dexmedetomidine group (group Dex).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The right sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread in NP and Dex groups.In group Dex,dexmedetomidine 50 μg/kg was injected intraperitoneally once a day starting from the end of operation until the animals were sacrificed.The equal volume of normal saline was given instead of dexmedetomidine in S and NP groups.Paw withdrawal threshold to von Frey filament stimulation (MWT) and paw withdrawal latency to thermal stimulation (TWL) were measured at 1 day before operation (To,baseline) and 5,9 and 16 days after operation (T1-3).Nine animals were sacrificed after measurement of pain threshold at T1-3 and their lumbar segments (L4,5) of the spinal cord were removed for detection of MMP-9 expression (by immuno-histochemistry) and tumor necrosis factor-alpha (TNF-α) content (by ELISA).Results Compared with group S,MWT was significantly decreased,TWL was shortened,and the levels of MMP-9 and TNF-α were increased at T1-3 in NP and Dex groups.Compared with NP group,MWT was significantly increased,TWL was prolonged,and the levels of MMP-9 and TNF-α were decreased at T1-3 in Dex group.Conclusion Dexmedetomidine can inhibit up-regulation of MMP-9 expression,and decrease inflammatory responses,thus attenuating NP in rats.

Objective To evaluate the effects of propofol on the expression of hippocampal γ-aminobutyric acid (GABAA) and NMDA receptor in a rat model of inflammatory pain (IP).Methods A total of 32 female Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups (n =8 each):control group (group C),group IP,and different doses of propofol groups (P1,2 groups).IP was induced by injection of formalin.In group C,normal saline and dimethyl sulfoxide (DMSO) 0.1 ml/kg were injected intraperitoneally.In group IP,normal saline and DMSO 0.1 ml/kg were injected intraperitoneally,and 5 min later formalin was injected.In P1,2 groups,propofol 30 and 100 mg/kg were intraperitoneally injected,respectively,and 5 min later formalin was injected.The pain behavior of rats was observed within 1 h after injection of formalin and pain intensity scoring (PIS) value was calculated.The animals were sacrificed at 1 h after injection of formalin and the hippocampi were isolated for determination of GABAA and NMDA receptor expression by immunohistochemisty.Results Compared with group C,PIS value was significantly increased,GABAA and NMDA receptor expression was up-regulated in IP and P1.2 groups.Compared with group IP,PIS value was significantly decreased,GABAA receptor expression was up-regulated,and NMDA receptor expression was down-regulated in P1,2 groups.PIS value was significantly lower,GABAA receptor expression was higher,and NMDA receptor expression was lower in group P2 than in group P1.Conclusion Intraperitoneal propofol can down-regulate NMDA receptor expression in hippocampi of rats with IP,thus inhibiting responses to pain sensitivity; intraperitoneal propofol can up-regulate hippocampal GABAA receptor expression,thus enhancing endogenous mechanism of analgesia.

Objective To determine the median effective dose (ED50) of hemocoagulase agkistrodon (HCA) inhibiting the bleeding after trans-bronchial lung biopsy (TBLB).Methods ASA physical status Ⅰ or Ⅱ patients of both sexes,aged 45-75 yr,body mass index 19-24 kg/m2,scheduled for elective TBLB,were enrolled in this study.TBLB was performed after routine anesthesia.HCA diluted in normal saline 5 ml was locally injected into the biopsy site at 2 min before surgery.The initial dose of HCA was 1.4 U.The dose of HCA was determined by up and down sequential method.Each time the dose of HCA increased/decreased in the next patient depending on whether nor not the bleeding was observed in the biopsy wound under fiberoptic bronchoscope.The ratio between the two successive concentrations was 1.2.The ED50 and 95 ％ confidence interval of HCA were calculated by Dixon's up-and-down method.Results ED50 of HCA inhibiting the bleeding after TBLB was 0.9 U,and 95 ％ confidence interval was 0.7-1.1 U.Conclusion ED50 of HCA inhibiting the bleeding after TBLB is 0.9 U.

Objective To screen cardiac-specific short-acting peptides on live myocardial slices using phage display technology,so as to improve the targeted delivery efficiency of drugs in myocardium and provide effective candidates for the targeted therapy of Duchenne muscular dystrophy (DMD) and other cardiomyopathies.Methods Myocardial tissue slices were prepared and cultured in vitro.The protein activities of the tissues were examined by immunohistochemistry.The in vitro cultured myocardial tissue slices were co-incubated with phage library (1×1012 pfu),and the phages that bound to the myocardium were recovered and amplified.The cardiac-specific targeting phages were identified by five rounds of in vitro phage biopanning.The candidate phage-related insertion sequence was sequenced,and the in vivo tissue distribution of the highly enriched phages was verified.Results A platform for in vitro culturing of live myocardial slices was established.Myocardial slices with good biological activity were obtained.After 48 hours of culturing,the normal expression and localization of Dystrophin protein were detected.Using phage library,candidate phages were screened after five rounds of phage biopanning.The results of the sequencing analyses and in vivo tissue distribution verification indicated that the selected candidate phages showed significant enrichment in myocardium and skeletal muscle,and showed low levels in liver and kidney tissues.Conclusions The candidate phages showed higher binding efficiency in both myocardium and skeletal muscle,indicating that the candidate peptides had myocardial targeting property,and that can provide a new method for myocardial targeting therapy of DMD.

Objective To evaluate the role of spinal AMP-activated protein kinase (AMPK) signaling pathway in reduction of neuropathic pain (NP) by dexmedetomidine in rats.Methods One hundred twenty adult male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into 4 groups (n=30 each) using a random number table: sham operation group (group S);group NP;dexmedetomidine group (group Dex) and AMPK inhibitor group (group AI).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The right sciatic nerve was exposed, and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread in NP and Dex groups.In group Dex, dexmedetomidine 50 μg/kg was injected intraperitoneally once a day starting from the end of operation until the animals were sacrificed.In group AI, AMPK inhibitor Compound C 20 mg/kg was injected intraperitoneally at the end of operation, and the other treatments were similar to those previously described in group Dex.The equal volume of normal saline was given instead of dexmedetomidine in S and NP groups.The mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before operation (baseline) and 2, 8 and 14 days after operation (T0-3).Results Compared with group S, the MWT was significantly decreased, and the TWL was shortened at T1-3 in NP, Dex and AI groups (P＜0.05).Compared with group NP, the MWT was significantly increased, and the TWL was prolonged at T1-3 in group Dex (P＜0.05) , and no significant change was found in MWT and TWL in group AI (P＞0.05).Conclusion Spinal AMPK signaling pathway is involved in reduction of NP by dexmedetomidine in rats.

Aim Toinvestigatewhetherexposureto Sanguinarine (SAN ) can inhibit cell proliferation in human mammary adenocarcinoma cells (MCF-7 ) and thepossiblemechanism.Methods WeexposedMCF-7 to anticancer compound SAN,cell viability was as-sessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT ) reduction assay. ROS was measured using confocal microscopy,expres-sion of caspase-3 ,caspase-8 and caspase-9 were calcu-latedusingchemiluminescencemethod.Results SAN remarkably inhibited growth of human mammary adeno-carcinoma MCF-7 cells by decreasing cell proliferation. ROS release and caspase-3,caspase-8,caspase-9 ex-pression were stimulated by SAN in MCF-7 ,and these changes were abolished by the antioxidant,N-acetyl-cysteine(NAC).Conclusion Regulationofcaspases expression and release from MCF-7 cells are possibly e-voked by SAN through reactive oxygen species.

Objective To evaluate the predictive accuracy of several risk-assessment strategies to predict the risk of significant neonatal hyperbilirubinemia, and to establish the best prediction model.Methods The transcutancous bilirubin (TcB) levels of 4907 term and near-team infants were measured.Trace blood bilirubin levels of the infants whose TcB levels ≥250 μmol/L were detected. Clinical data of newborns and their mothers were collected and were analyzed with Logistic regression model to investigate its correlation with signifrcant hyperbilirubinemia. Clinical high risk factors of significant neonatal hyperbilirubinemia were determined. Accuracy of three prediction methods for significant hyperbilirubinemia was compared by receiver operating characteristic (ROC) curve. The three methods included: whether predischarge bilirubin level (within 72 hours after birth) expressed in risk zone on an hour-specific bilirubin nomogram; clinical risk factors other than predischarge bilirubin level; and combination of the predischarge bilirubin risk zone and other clinical risk factors. Results Two hundred and eighty-six newborns (5.8%) were found with significant hyperbilirubinemia. The risk factors of significant neonatal hyperbilirubinemia were divided into three groups according to OR: (1) Major risk factors:predischarge (within 72 hours after birth) bilirubin level in the high risk-zone (OR=96. 39, 95% CI:53.32-174.27, P = 0. 000), large cephalohematoma (OR = 36.45, 95% CI: 10. 02-132.56,P=0. 0076), gestational age 35-36+6 weeks (OR= 30. 72, 95% CI 14.47-65.23, P=0. 0001) and exclusive breast feeding and weight loss was ＞9% of birth-weight (OR=22.44, 95% CI: 4.42-114. 03, P=0. 0016). (2) Minor risk factors: gestational age 37-37+6 weeks (OR=3.26, 95% CI:1.92-5. 55, P=0. 0232), predischarge bilirubin level in P76-P95(OR=13. 64, 95% CI: 8. 10-22.97,P=0. 0001) and bruising (OR = 2.32, 95% CI: 1.14-4.71, P = 0. 0497). (3)Protective factors (those factors associated with decreased risk of hyperbilirubinemia): predischarge bilirubin level in low-risk zone (≤P40) (OR=0. 00), gestational age ≥40 weeks (OR=0.21, 95% CI: 0.09-0.44,P=0. 0402) and mixed breeding (OR=0. 75, 95% CI: 0. 58-0.95, P=0.0059). The area under the ROC curve of predischarge bilirubin level was 0. 8687 and 0. 7375 for clinical risk factors other than predischarge bilirubin level. The area under the ROC curve of a combination of the predischarge bilirubin risk zone and additional clinical risk factors was 0. 9367. Conclusions The risk of significant neonatal hyperbilirubinemia could be simply and accurately predicted by infant's predischarge bilirubin level and the combination of predischarge bilirubin level, and clinical risk factors might improve the accuracy of prediction significantly.

Objective To systematically evaluate the effectiveness of delayed cord clamping (DCC) in term infants. Methods The data of the Cochrane library, PubMed, EMBASE, CNKI , VIP, Wanfang from 1 January 1970 to 30 April 2013 were searched. Randomized controlled trials (RCT) of DCC in term infants were included.RevMan 5.1.0 was used in the statis-tical analysis. Results Ten studies involving 1623 participants were included. Meta-analysis based on included studies showed that:compared with immediate cord clamping (ICC), DCC improved the hemoglobin levels at birth (MD=2.19, 95%CI:0.36, 4.02) and increased the incidence of polycythaemia (RR=2.87, 95%CI:1.24, 6.62). Compared with ICC, DCC showed no signi-ficant difference in the phototherapy for hyperbilirubinemia (RR=2.46, 95%CI: 0.93, 6.52), the hemoglobin levels within 6 months (MD=0.29, 95%CI:-0.17, 0.75), and the incidence of anemia (RR=0.71, 95%CI:0.45, 1.12). Conclusions DCC can improve the hemoglobin level in term infants after birth. However, the appropriate time of cord clamping has not been deter-mined. It is necessary to undertake further studies with higher quality and larger scale to evaluate the optimal time of cord clam-ping.

Objective To study the efficacy of T-piece resuscitator on the very preterm infants in the delivery room.Method Very preterm infants (gestational age 28 ～ 31 weeks) who needed positive pressure ventilation during delivery room resuscitation were included in the study between January 2010 and December 2015.Enrolled infants were randomly assigned to self-inflating bag group and T-piece group.Tracheal intubation ratio,duration of mechanical ventilation,continuous positive airway pressure (CPAP),supplementary oxygen through a nasal cannula and total oxygen requirement were compared between groups.The percentages of pneumothorax,sepsis,necrotizing enterocolitis (NEC),bronchopulmonary dysplasia (BPD),retinopathy of prematurity (ROP),intracranial hemorrhage and patent ductus arteriosus (PDA) between groups were also compared.Data were analyzed using independent sample t test and chi-square test.Result A total of 51 preterm infants were enrolled in this study,with 25 infants in the self-inflating bag group and 26 in the T-piece group.There was no statistically significant difference in the gender,gestational age,birth weight,Apgar scores,delivery mode and antenatal glucocorticoids between the two groups (P ＞ 0.05).The ratio of intubation in T-piece group was significantly lower than that in self-inflating bag group (15.4％ vs.44.0％,P ＜ 0.05).Further more,duration of mechanical ventilation and total oxygen requirement in the T-piece group were significantly shorter than those in the self-inflating bag group [(4.2±2.8) dvs.(10.1 ±4.3) d,(36.2±14.7) dvs.(47.2±19.2) d,P＜0.05].However,the duration of nasal CPAP and supplementary oxygen through a nasal cannula,the rate of pneumothorax,sepsis,NEC,BPD,ROP,intracranial hemorrhage and PDA did not differ significantly between groups (P ＞ 0.05).Conclusion Compared with the self-inflating bag group,the use of the T-piece in delivery room decrease the rate of tracheal intubation and the duration of mechanical ventilation and total oxygen requirement.

Objective To determine the effects of feeding donor human milk versus formula milk on very low birth weight infants (VLBWI) and extremely low birth weight infants (ELBWI).Methods The Cochrane library,PubMed,EMBASE,Wanfang,CNKI and VIP database were searched for the randomized controlled trials (RCT) that compare donor human milk with formula milk in VLBWI and ELBWI from the establishment of database up to February 2014.The quality of the included studies was assessed.Meta analysis was performed using RevMan 5.2.9 software.The results were expressed by mean difference (MD) and 95％CI for continuous variables,RR and 95％CI for categorical variables.Results Only five trials were included:in quality evaluation,two trials were graded B,and the other three were graded C.Meta-analysis showed that,compared with the formula milk,feeding of donor human milk could reduce the risk ofnecrotizing enterocolitis (RR=0.36,95％CI:0.18-0.73,P＜0.01),but not the risks of sepsis (RR=0.92,95％CI:0.50 1.72,P=0.80),retinopathy of prematurity (RR=1.21,95％CI:0.84-1.74,P=0.31) and in-hospital mortality (RR=0.66,95％CI:0.18-2.37,P=0.52).The significantly lower rates in weight gains in neonatal period (MD=-6.58,95％CI:-11.19 to-1.98,P＜0.01) and body length (MD=-0.30,95％CI:-0.41 to-0.20,P＜0.01)were found in donor human milk compared with formula milk.No significant difference in head circumference (MD=-0.16,95％CI:-0.33 to 0.01,P=0.13) was seen in comparison of donor human milk with formula milk.Conclusions Feeding with donor human milk can reduce the risk ofnecrotizing enterocolitis in VLBWI and ELBWI,but its effects on neonatal growth need to be further studied in large scale RCT.