Objective To explore the relationship between brain development and early behavior development of infant rats. Methods Infant Spraque - Dawley(SD) rats were used respectively for testing their spontaneous behaviors, inhibitory escaping response and behavior development, and also determine their brain weight and content of Zinc in different part of the brain at age of 1 day, 11 days and 21 days. Results There was a positive correlation between brain development and early behavior development of SD rat, and the high content of zinc in hippocampus and cerebellum. Conclusion It is suggested that the high content of Zinc guarantee furnish security for the late behavior development of infant rat.

Objective To explore the effects of penehyclidine hydrochloride (PHC) on the withdrawal syndrome and conditioned place preference(CPP) of morphine dependent rats. Methods ( 1 ) Forty-eight male SD rats were randomly assigned to 6 groups with one of 8 rats:morphine dependent group (MOR group) ,naloxone precipitated withdrawal group ( NAL group) ,PHC treatment groups ( PHC1,2,3 ) ,normal saline control group ( NS group). Subcutaneous injection of morphine in gradually increasing doses for 5 days (from 10 to 50 mg/kg ,two times daily) to establish the model of morphine physical dependent rats. The withdrawal syndrome was precipitated by naloxone (5 mg/kg,sc) and treated with PHC in various doses (0.5,1.0,1.5 mg/kg ,ip ) 30 min before haloxone-precipitated withdrawal. The body weight loss and withdrawal syndrome were observed respectively in 20 minutes. (2) 40 male SD rats were randomly assigned to 5 groups with one of 8 rats: morphine dependent group (MOR group) ,PHC treatment groups (PHC1 ,2,3 ) ,normal saline control group (NS group). The morphine conditioned place preference was induced by alternate subcutaneous injection of morphine for 7 days in rats ( 10mg/kg,once daily,8:00 AM) and saline( 16:00 PM). At d8,the rats were received the CPP test. The rats of PHC groups were treated with PHC (0.5,1.0,1.5 mg/kg , ip) prior to the CPP test, whereas the rats were treated with saline in MOR and NS group. Results (1) Theweight loss((8.53 ±l.20)g,(7.36±l.06)g,(5.40±1.79 ) g vs ( 12.63 ± 2.22 ) g, F = 83.16, P ＜ 0.01 ) and score precipitated withdrawal symptoms ( 25.36 ± 3.11,21.38±3.50,17.06±1.78 vs 31.69 ±2.76, F=256.56, P＜0.01)of morphine withdrawal rats was obviously alleviated by ip PHC in dose-related manner before naloxone-precipitated withdrawal. (2) There were significant differences in the times spent in the drug-paired side (gray area) between MOR and PHC groups( (529 ± 83 )s,(460 ± 107 ) s, (418 ± 97 ) s vs ( 643 ± 111 ) s, F = 13.22, P ＜ 0.01 ), and also in dose-related manner. Conclusion PHC could significantly inhibit the withdrawal syndrome and the expression of CPP on morphine dependent rats in a dose-dependent manner.

Objective:To investigate the relationship between EGFR mutations and pulmonary tuberculosis in lung adenocarcino-ma. Methods:We detected EGFR mutations in 506 patients with lung adenocarcinoma by PCR amplification and sequencing and ana-lyzed the relationship between the mutations observed and pulmonary tuberculosis. Survival analysis was performed using the Ka-plan-Meier method with log-rank tests. Result:A total of 218 patients showed EGFR mutations;of these patients, 25 had a clinical his-tory of pulmonary tuberculosis. Compared with lung adenocarcinoma patients with no history of tuberculosis, patients with a history of pulmonary tuberculosis showed higher incidence rates of EGFR mutations, especially of exon 21 (P=0.047, P=0.002). Higher incidence rates of EGFR mutations, especially of exon 21, were observed in patients with lung cancer and tuberculosis in the same lobe or the same side of the lung than in those who had lung cancer and tuberculosis in opposite sides of the lung (P=0.02, P=0.03). Survival analy-sis showed that adenocarcinoma patients with a history of pulmonary tuberculosis have 2-year survival rates lower than that of adeno-carcinoma patients with no history of the disease (P=0.039). In patients adenocarcinoma associated with tuberculosis patients without EGFR-TKIs treatment, the 2-year survival rates of EGFR mutation patients and those without EGFR mutation showed no statistically significant difference (P=0.948). At the same time, we got the same results in adenocarcinoma associated with tuberculosis patients with EGFR-TKIs treatment (P=0.425). Conclusion:Lung adenocarcinoma patients with a history of pulmonary tuberculosis have high-er incidence rates of EGFR mutations, and EGFR mutations are not related to disease prognosis.

Objective To evaluate the effect of dexmnedetomidine pretreatment on apoptosis in hippocampal neurons of rats undergoing one-lung ventilation (OLV).Methods Ninety adult male SpragueDawley rats,aged 10-11 months,weighing 260-300 g,were divided into 3 groups (n=30 each) using a random number table:two-lung ventilation (TLV) group,group OLV and dexmedetomidine pretreatment group (group D).Dexmedetomidine 25 μg/kg was injected intraperitoneally at 45 min before OLV in group D.After tracheal intubation,the animals were ventilated in volume-controlled mode.OLV was performed for 90 mnin followed by 30 min of TLV in OLV and D groups.TLV was performed for 120 min in group TLV.On 1,3 and 7 days after ventilation,6 rats in each group were selected,and Morris water maze test was carried out to evaluate the cognitive function.The swimming speed,time of staying at the target quadrant,and frequency of crossing the platform quadrant were recorded.Six rats in each group were selected immediately after ventilation and sacrificed,the hippocampi were removed for detection of cell apoptosis,and the apoptosis index was calculated.Immediately after ventilation and on 1,3 and 7 days after ventilation,6 rats in each group were selected and sacrificed,and the hippocampi were removed for determination of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2),phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB),Bcl-2 and Bax expression.The ratio of Bcl-2 expression to Bax expression (Bcl-2/Bax ratio) was calculated.Results Compared with group TLV,the time of staying at the target quadrant was significantly shortened,the frequency of crossing the platform quadrant was decreased,the apoptosis index was increased,the expression of pERK1,pERK2,pCREB and Bcl-2 was down-regulated,the expression of Bax was up-regulated,and Bcl-2/Bax ratio was decreased in group OLV (P＜0.05 or 0.01).Compared with group OLV,the time of staying at the target quadrant was significantly prolonged,the frequency of crossing the platform quadrant was increased,the apoptosis index was decreased,the expression of pERK1,pERK2,pCREB and Bcl-2 was up-regulated,the expression of Bax was down-regulated,and Bcl-2/Bax ratio was increased in group D (P＜0.05 or 0.01).Conclusion Dexmedetomidine pretreatment decreases apoptosis in hippocampal neurons through activating ERK/CREB signaling pathway,thus reducing cognitive dysfunction of rats undergoing OLV.

Objective To investigate the effect of penehyclidine hydrochloride (PHCD) on the reinstatement of conditioned place preference (CPP) in morphine dependent rats. Methods Forty male adult SD rats weighing 180-220 g were randomly divided into 5 groups (n = 8 each): group control (group C); group morphine (group M) and 3 PHCD groups (group P1-3 ). Morphine 10 mg/kg was injected subcutaneously once a day for 8 days to induce morphine CPP. The rats were then subjected to extinction of CPP for 10 days with normal saline (NS) instead of morphine. After the extinction, the rats were put into the drug-paired side of the box. A single priming dose of morphine 4 mg/kg was injected to reinstate the morphine CPP. In group P1-3 the rats received PHCD 0.5, 1.0 and 1.5 mg/kg intraperitoneally 30 min prior to priming dose of morphine, whereas in group C and M the rats received NS. The second day the rats underwent CPP test. Results Compared with group M, the time spent in the drug-paired side (grey area) was significantly shortened in group P1-3 (P ＜ 0.05 or 0.01 ).Compared with group P1 ,no significant change in the time spent in the drug-paired side (grey area) was found in group P2(P ＞ 0.05), but the time spent in the drug-paired side (grey area) was significantly shortened in group P3 ( P ＜ 0.05). Conclusion PHCD could significantly inhibit the reinstatement of CPP induced by priming dose of morphine in morphine dependent rats and it is related to the dose.

Objective To investigate the efficacy of relaparoscopic common bile duct exploration in choledocholithiasis.Methods 50 patients who underwent LC/OC/LCBDE/OCBDE for biliary surgery with choledocholithiasis were randomized into two groups:Group A (n ＝25) laparoscopic approach and Group B (n =25) open approach.The operation time,hospital stay,cost of hospitalization and postoperative complications were compared.Results There was no significant difference in the operation time,liver functional index,postoperative bile leakage rate and cost of hospitalization between the two groups.The postoperative hospital stay in group A was shorter than that in group B (7.1 ± 1.5 vs 12.4 ±4.3 days,P ＜0.05),as was the volume of intraoperative blood loss (58.3 ± 24.2 ml vs 108.6 ± 35.7 ml,P ＜ 0.05),recovery of gastrointestinal function (26.3 ±3.6 vs 58.2 ±6.3 hours,P ＜0.05),postoperative analgesia (7/25 vs 17/25,P＜0.05) and wound infection rate (1/25 vs 6/25,P＜0.05).Conclusions Relaparoscopic commonbile duct exploration for recurrent choledocholithiasis appeared to be a safe,feasible,and efficacious procedure when carried out by expert laparoscopic surgeons.The procedure is worth promoting.

Objective To study the effect of different dialysis modalities on pruritus in elderly maintenance hemodialysis patients.Methods Totally 51 patients were randomly divided into hemoperfusion combined with hemodialysis group (HD+ HP),hemodiafiltration group (HDF) and hemodialysis group (HD).Plasma β2-microglobulin(β2-MG) and intact parathyroid hormone (iPTH) were measured by means of radio immunoassay at pre and post dialysis,4 weeks and 8 weeks after dialysis,cutaneous pruritus was scored.The remission rate of itching was calculated at 8 weeks after dialysis.The parameters were compared among different groups.Results The level of plasma β2-MG was lower in HD+HP group after dialysis than pre dialysis [(13.48±3.05)mg/L vs.(16.27±4.73) mg/L,t＝2.044,P＜0.05],at 4 weeks and 8 weeks after dialysis,its levels were decreased to (10.97±3.25)mg/L(t＝3.808,P＝0.002)and (6.47±2.35)mg/L(t＝7.650,P＝0.000),respectively.The levels of iPTH were also found decrease from(887.5 ± 242.7)ng/L to (688.3 ±223.4)ng/L(t＝3.384,P＝0.004)at 4 weeks and (467.2±102.5) ng/L(t＝6.578,P＝0.000) at 8weeks after dialysis in HD+HP group (all P＜0.01).There were differences of the levels of plasma β2-MG and iPTH at 4 weeks and 8 weeks after dialysis in HDF group (all P＜ 0.05),but no differences of the levels of plasma β2-MG and iPTH during every period were found in HD group(all P＞0.05).The scores of cutaneous pruritus were decreased from (21.17± 5.01) scores to (13.37±2.85) scores(t＝ 5.580,P＝0.000)at 4 weeks and (8.52±4.38) scores(t＝7.838,P＝0.000)at 8 weeks after dialysis in HD+ HP group,and also the scores at 4 and 8 weeks after dialysis in HDF group (all P＜0.01),but there were no significant differences of the scores during every period in HD group (all P＞0.05).The remission rate of itching was better in HD+ HP group than in HDF group [88.24％ (15/17 cases) vs.58.82％ (10/17 cases),x2＝14.44,P＝0.000],better in HDF group than in HD group 23.53％ (4/17 cases) (x2 ＝4.37,P＝0.037).Conclusions HD+HP is superior to HDF in efficiently clear β2-MG and iPTH,and relief cutaneous pruritus,but HD can poorly clear β2-MG and iPTH or relief itching.

Objective To investigate the effect of penehyclidine hydrochloride (PHCD) on tramadol dependence and c-fos,△ FosB and M5 receptor expression in relevant brain regions in rats.Methods Thirty male adult SD rats weighing 180-220 g were randomly assigned to 3 groups (n =10 each):control group (group C),tramadol dependence group (group T) and PHCD group (group P).Tramadol dependence was induced by subcutaneous 10 mg/kg once a day for 7 consecutive days in groups T and P.PHCD 1.5 mg/kg was injected intraperitoneally on day 8 in group P,while in groups C and T the equal volume of normal saline was injected intraperitoneally instead of PHCD.The rats underwent conditioned place perference test at 30 min after intraperitoneal injection.The time spent in drug-paired side (gray area) was recorded.The rats were sacrificed after the conditioned place perference testand the brain was removed.The relevant brain regions (ventral tegmental area,prefrontal cortex,nucleus accumbens )were separated for determination of c-fos,△ FosB expression by Western blot and M5 receptor mRNA expression by RT-PCR.Results Compared with group C,the time spent in the drug-paired side (gray area) was significantly prolonged,and c-fos,△FosB and M5 receptor mRNA expressions were up-regulated in group T,△FosB and Ms receptor mRNA expressions were down-regulated in group P ( P ＜ 0.05 or 0.01 ).There was no significant difference in time spent in the drug-paired side (gray area) and c-fos expression between groups C and P( P ＞ 0.05).Compared with group T,the time spent in the drug-paired side (gray area) was significantly shortened,and c-fos,△ FosB and M5 receptor mRNA expressions were down-regulated in group P (P ＜0.01).Conclusion PHCD can significantly inhibit tramadol dependence by down-regulating c-fos,△FosB and M5 receptor expression in relevant brain regions.

Objective To investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) in attenuation of lipopolysaccharide (LPS)-induced human umbilical vein endothelial cell injury by penehyclidine hydrochloride (PHC).Methods Human umbilical vein endothelial cells were provided by Medical Research Center,Wuhan University,cultured and seeded in 96-well plate (100 μl/hole) or 24-well plate (3 nl/hole) with density of 1 × 104/ml or in culture flasks (5 ml/flask) with density of 1 × 106/ml.The cells were randomly divided into 4 groups ( n =23 each):group control (group C) ; group LPS; group PHC (group P) and group PHC + LPS (group PL).The cells were exposed to LPS 1 μg/ml in groups L and PL or/and PHC 2 μg/ml in groups P and PL.LPS was added at 1 h after PHC in group PL.The cells were collected at 24 h exposure to LPS for determination of the expression of phosphorylated p38 MAPK (p-p38 MAPK) and p38 MAPK.The ratio between p-p38 MAPK and p38 MAPK was calculated.Cell viability,NO content and inducible nitric oxide synthase (iNOS) expression were also determined.Results LPS significantly decreased cell viability,increased NO content,iNOS expression,p-p38 MAPK and p-p38 MAPK/p38 MAPK ratio in group L as compared with group C.In group PL pretreatment with PHC significantly attenuated LPS-induced cell injury.Conclusion p38 MAPK pathway is involved in attenuation of LPS-induced endothelial cell injury by PHC.

Objective To investigate the effects of penehyclidine hydrochloric(PHC)pretreatment on the expression of β-arrestin-2 in the lung tissue in sepsis-induced acute lung injury in mice.Methods Thirty female Ktmming mice,aged 6 weeks,weighing 18-20 g,were randomly divided into 3 groups(n =10 each):sham operation group(group S); sepsis group(group CLP)and penehyclidine hydrochloric pretreatment group(group PHC).Sepsis was induced by cecal ligation and puncture(CLP)in groups CLP and PHC.Penehyclidine hydrochloric 0.45 mg/kg was injected intraperitoneally at 1 h before CLP in group PHC.While the equal volume of normal saline was given instead of penehyclidine hydrochloric in groups S and CLP.At 12 h of CLP,the animals were sacrificed,and the lung tissues were removed for determination of MPO activity(by colorimetry),IL-6 content(by ELISA),β-arrestin-2 mRNA and protein expression(by RT-PCR and Western blot respectively).Blood samples and bronchoalveolar lavage fluid were collected to calculate pulmonary vascular permeability index(PV PI).Results Compared with group S,PVPI,IL-6 content and MPO activity were significantly increased,the expression of β-arrcstin-2 protein was significantly down-regulaled while the expression of β-arrestin-2 mRNA was up-regulated in group CLP,and PVPI,IL-6 content and MPO activity were significantly incrcased,the expression of β-arrestin-2 protein was significantly up-regulated,while the expression of β-arrestin-2 mRNA was down-regulated in group PHC(P ＜ 0.05).Compared with group CLP,PVPI,IL-6 content,and MPO activity were significantly decreased,the expression of β-arrestin-2 protein was significantly up-regulated,while the expression of β-arrestin-2 mRNA was dow n-regulated in group PHC(P ＜ 0.05).Conclusion PHC pretreatment can attenuate the lung injury induced by sepsis in mice through up-regulating the expression of β-arrestin-2 protein.