Structure of natural product-ursolic acid was modified for increasing its antitumor activity. Ursolic acid was acylated, esterified, hydrolized or oxidized to obtain target pentacyclic triterpenoid compounds with different substitutes. Sixteen derivatives of ursolic acid were designed and synthesized including eleven new compounds. Anti-tumor activities of ursolic acid and these derivatives against HeLa, SKOV3 and BGC-823 cells in vitro were investigated by MTT assay. The results indicated that compounds 7a and 8a were found to have stronger cell growth inhibitory than ursolic acid on HeLa cells and SKOV3 cells separately, and are worth to be intensively studied further.

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) pretreatment on NF-κB mRNA expression and SOD activity in lung tissues in rats with acute lung injury (ALI) induced by LPS.Methods Thirty-two male SD rats, 2 months old, weighing 230-280 g, were randomly divided into 4 groups (n=8 each): control group (group C), ALI group, low dose PHCD group (group LP) and high dose PHCD group (group HP). ALI was induced by intravenous LPS 5 mg/kg via tail vein. Group LP and HP received intraperitoneal PHCD 0. 3 and 1 mg/kg respectively 30 min before LPS administration. The rats were killed at 6 h after LPS administration. The lungs were removed immediately for determination of W/D lung weight ratio, lung water content, NF-κB mRNA expression, TNF-α and MDA content, and SOD activity and microscopic examination. Results NF-κB mRNA expression, TNF-α and MDA content, W/D lung weight ratio and lung water content were significantly higher, while SOD activity was significantly lower in group ALI, LP and HP than in group C (P ＜ 0.05). NF-κB mRNA expression, TNF-α and MDA content, W/D lung weight ratio and lung water content were significantly lower, while SOD activity was significantly higher in group LP and HP than in group ALI and HP than in group LP (P ＜ 0.05). The LPS-induced changes were mitigated by pretreatment with low and high doses of PHCD in group LP and HP.Conclusion Pretreatment with PHCD attenuates LPS-induced ALI by downregulating NF-κB mRNA expression, decreasing local inflammatory response and enhancing anti-oxidant activity.

With the progress of visualization technology, more and more visual tools were applied to anesthesia. It has accurate positioning, mild trauma, a high success rate and less complications for endotracheal intubation, which increase the safety and efficiency of airway management. Disposcope endoscope is an endotracheal intubation tool with a visual stylet, which has many advantages, such as visual, lens barrel can be bent and wireless transmission. This paper summarizes the current progress in the application of Disposcope endoscopy in tracheal intubation.

Objective To evaluate the effect of hydrogen on the activation of caspase-3 in brain tissues during cerebral ischemia-reperfusion (I/R) in rats.Methods Thirty-six healthy adult male Sprague-Dawley rats,weighing 220-250 g,were divided into 3 groups (n=12 each) using a random number table:sham operation (group S),I/R group and hydrogen group (group H).Cerebral ischemia was induced by occlusion of the middle cerebral artery followed by reperfusion in I/R and H groups.In group H,hydrogen-rich saline 5 ml/kg (0.6 mmol/L) was injected intraperitoneally at 3 days before establishment of the model and immediately after the onset of reperfusion.At 24 h of reperfusion,the rats were sacrificed,and hippocampal tissues were obtained for determination of neuroapoptosis (by TUNEL),apoptotic neuron count and expression of activated caspase-3 (by Western blot).The brain tissues in the ischemic area were obtained and stained with haematoxylin and eosin for examination of the pathological changes.Results Compared with group S,the expression of activated caspase-3 was significantly up-regulated,and the apoptotic neuron count was increased in I/R and H groups (P<0.05).Compared with group I/R,the expression of activated caspase-3 was significantly down-regulated,the apoptotic neuron count was decreased (P<0.05),and the pathological changes of brain tissues were significantly reduced in group H.Conclusion The mechanism by which hydrogen inhibits neuroapoptosis during cerebral I/R is probably related to inhibited activation of caspase-3 in brain tissues of rats.

Objective To evaluate the effect of hydrogen-rich saline on the expression of phosphor-p38 mitogen-activated protein kinase (p-p38MAPK) during cerebral ischemia-reperfusion (I/R) in rats.Methods Seventy-two adult male Sprague-Dawley rats,weighing 220-250 g,were randomly divided into 3 groups (n =20 each) using a random number table:sham operation group (group S),I/R group and hydrogen-rich saline group (group I/RH).Cerebral ischemia was induced in chloral hydrate-anesthetized rats by 2 h middle cerebral artery occlusion in I/R and I/RH groups.The artery was only exposed but not occluded in group S.At 3 days before operation and immediately after onset of reperfusion,hydrogen-rich saline (0.6 mmol/L) 10 ml/kg was intraperitoneally injected in group I/RH,while the equal volume of normal saline was given in S and I/R groups.Neurological deficits were blindly assessed and scored at the end of 24 h reperfusion.The animals were then sacrificed,and brains were removed for microscopic examination and for determination of the cerebral infarct size (by TTC),brain water content,cell apoptosis (by TUNEL),and expression of p38MAPk and phosphor-p38MAPK (p-p38MAPK) (by immunohistochemistry and Western blot).Apoptosis index was calculated.Results Compared with group S,neurological deficit score,apoptosis index,brain water content and cerebral infarct size were significantly increased,and the expression of p38MAPK and p-p38MAPK was up-regulated in I/R and I/RH groups.Compared with group I/R,neurological deficit score,apoptosis index,brain water content and cerebral infarct size were significantly decreased,and the expression of p38MAPK and p-p38MAPK was down-regulated in group I/RH.The pathological changes of cerebral tissues were significantly attenuated in group I/RH as compared with group I/R.Conclusion Hydrogen-rich saline can reduce cell apoptosis through inhibiting p-p38MAPK expression,thus attenuating cerebral I/R injury in rats.

Objective To explore the protective effects of dipeptidyl peptidase-4 inhibitor (DPP-4I) on AD-like neurodegenerative changes and its mechanism. Methods The human neuroblastoma cell line SH-SY5Y on the logarithmic phase was divided into six groups:control group (CON group, treated with PBS contained 1‰DMSO for 12 h), wortmannin intervention group (W group, treated with 0.03 μmol/L wortmannin for 12 h), DPP-4I intervention group (DPP-4I group, treated with 10μmol/L DPP-4I for 12 h), both DPP-4I and wortmannin intervention group (DPP-4I+W group, pre-treated with 10 μmol/L DPP-4I for 2 h, then 0.03 μmol/L wortmannin for 12 h), DPP-4I, wortmannin and Ex9-39 intervention group (DPP-4I+W+Ex9-39 group, pre-treated with 10μmol/L Ex9-39 for 2 h, then 10μmol/L DPP-4I for 2 h followed by 0.03μmol/L wortmannin for 12 h), and Ex9-39 intervention group (Ex9-39 group, treated with 10μmol/L Ex9-39 for 12 h). MTT assay was used to detect the cell vitality. Western blot assay was used to detect the level of total tau protein (tau-5) and phosphorylated tau at different sites (pSpS199/202, pT231 and pS396), the level of phosphorylated neurofilaments (NF-H, NF-M) and phosphorylation of critical enzyme in PI3K/Akt/GSK-3β signaling pathway. Results (1) The cell vitality decreased, the levels of pSpS199/202, pT231, pS396 and NF-H/M increased significantly in W group than those in CON group. However, comparing with CON group, the above mentioned parameters reversed in DPP-4I group. Comparing with W group, the cell vitality increased and phosphorylated levels of above mentioned indices were decreased in DPP-4I+W group. (2) The cell vitality showed a decline trend while the levels of phosphorylation tau at three different sites and NF-H/M were higher in Ex9-39 group than those in CON group. Comparing with DPP-4I+W group, the results of the phosphorylated levels showed the same changes in DPP-4I+W+Ex9-39 group. (3) Comparing with CON group, the expression levels of phosphorylated PI3K, Akt and GSK3β increased significantly in DPP-4I group, while those decreased in W group. Additionally, the expression levels of phosphorylated PI3K, Akt and GSK3β were significantly increased in DPP-4I+W group than those in W group. Conclusion DPP-4I can enhance the level of GLP-1 and activate PI3K/Akt/GSK-3βinsulin signaling pathway to improve the hyperphosphorylated tau and NFs induced by wortmannin, and to protect AD-like neurodegeneration.

Objective To retrospectively investigate the incidence of accidental awareness during general anesthesia in selective operation and analyze the influence factors of accidental aware-ness.Methods Patients scheduled for elective surgery requiring general anesthesia with artificial air-way during April 2013-July 2015 were collected.The incidence was obtained from postoperative fol-low-ups.Perioperative data and anesthetic drugs were collected to analyze influence factors. Results A total of 141 294 patients were enrolled.Eighty patients (0.06%)were definitely identified as awareness.Multiple regression analysis showed that awareness during operation was associated with total intravenous anesthesia (OR=5.181,95% CI 3.032-8.853),using laryngeal mask airway (OR=2.478,95% CI 1.544-3.977)and ASA Ⅲ or Ⅳ (OR=9.202,95% CI 5.475-15.466).Pre-medication of midazolam (OR=0.125,95% CI 0.080-0.196)and combination of sevoflurane (OR=0.193,95% CI 0.113-0.330)had lower incidence of awareness during operation.Conclusion Total intravenous anesthesia,using laryngeal mask airway and ASA Ⅲ or Ⅳ are risk factors of accidental awareness during general anesthesia.Premedication of midazolam and combination of sevoflurane may prevent awareness during operation.

Objective To evaluate the effect of hydrogen-rich saline on inflammatory responses during transient cerebral ischemia-reperfusion (I/R) in rats.Methods Forty-five male Sprague-Dawley rats,aged 5-6 yr,weighing 180-250 g,were randomly divided into 3 groups (n =15 each) using a random number table:sham operation group (group S),group I/R and hydrogen-rich saline group (group H).The rats were anesthetized with intraperitoneal 10％ chloral hydrate 0.3 ml/100 g.Transient cerebral ischemia was induced by bilateral common carotid artery occlusion with hypotension for 15 min,followed by reperfusion.Five rats were randomly chosen from each group,and Morris water maze was used to assess the cognitive function starting from 5 days before establishment of the model.Place navigation test lasted for 5 consecutive days.The escape latency,swimming speed and swimming distance were recorded.Spatial probe test was carried out on 1 and 3 days after establishment of the model.The time of staying at the target platform quadrant,frequency of crossing the original platform and swimming speed were recorded.The rats were sacrificed after the end of spatial probe test on 3 days after the model was established,and hippocampi were removed to examine the morphology of neurons in hippocampal CA1 region with light microscope.Five rats randomly chosen from each group were sacrificed on 1 day after the model was established,and hippocampi were removed to detect the contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β).The rest 5 rats in each group were sacrificed,and hippocampi were removed for determination of nuclear factor kappa B (NF-κB) activity (by immuno-histochemistry).Results In place navigation test before the model was established,the escape latency and swimming distance were gradually shortened with the prolonging training time,and no significant change was found in the swimming speed with the prolonging training time in the three groups.Compared with group S,the time of staying at the target platform quadrant was significantly shortened,and the frequency of crossing the original platform was reduced on 1 and 3 days after establishment of the model,and the contents of TNF-α and IL-1β and NF-κB activity were increased on 1 day after establishment of the model in group I/R.Compared with group I/R,the time of staying at the target platform quadrant was significantly prolonged,and the frequency of crossing the original platform was increased on 1 and 3 days after establishment of the model,and the contents of TNF-α and IL-1β and NF-κB activity were decreased on 1 day after establishment of the model in group H.There was no significant change in the swimming speed during spatial probe test on 1 and 3 days after establishment of the model.Conclusion The mechanism by which hydrogen-rich saline reduces transient cerebral I/R injury may be related to inhibition of inflammatory responses in rats.

Objective To evaluate the effect of thoracic paravertebral block (TPVB) on inflammatory responses in the patients undergoing thoracoscopic radical resection of lung cancer with general anesthesia.Methods Eighty patients of both sexes,aged 18-64 yr,with body mass index of 18-24 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective thoracoscopic radical resection of lung cancer,were divided into 2 groups (n =40 each) using a random number table method:control group (group C) and TPVB group.Ultrasound-guided TPVB was performed with 0.5％ ropivacaine 10 ml which was injected into the paravertebral space of T4,7 at 30 min before anesthesia induction in group T.Patient-controlled intravenous analgesia (PCIA) was performed at the end of surgery.When visual analogue scale score＞3,morphine 5-10 mg was intravenously injected.Venous blood samples were collected immediately before surgery (T0) and at 12,24 and 48 h after surgery (T1-3) for determination of serum interleukin-6 (IL-6) and IL-10 concentrations by enzyme-linked immunosorbent assay.The pressing times of PCIA and total volume of fluid infused were recorded at T2,3.The patients were followed up for 48 h after surgery,the development of nausea and vomiting,somnolence and pruritus was recorded,and the total occurrence of adverse reactions was calculated.Results Compared with group C,the pressing times of PCIA and total volume of fluid infused were significantly decreased at T2,3,the incidence of nausea and vomiting,total incidence of adverse reactions and the number of cases required morphine were decreased,and the serum concentration of IL-6 was decreased and the serum concentration of IL-10 was increased at T1-3 in group T (P＜0.05).Conclusion TPVB can alleviate inflammatory responses in the patients undergoing thoracoscopic radical resection of lung cancer with general anesthesia.

Objective To evaluate the effect of dexmedetomidine on sevoflurane anesthesia-in-duced cortical epileptiform electroencephalogram ( EEG) activity in the neonatal rats. Methods Forty clean-grade healthy Sprague-Dawley rats, aged 4-6 days, weighing 8-15 g, were divided into 5 groups (n＝8 each) using a random number table method: control group ( C group), sevoflurane group ( S group), dexmedetomidine plus sevoflurane group (D+S group), dexmedetomidine plus alpha 2-adrenocep-tor antagonist atipamezole plus sevoflurane group (D+A+S group), and atipamezole plus sevoflurane group (A+S group). After the electrode was correctly placed, the EEG was continuously monitored, and normal saline 5 μl∕g was intraperitoneally injected at 58 min of monitoring in group C, dexmedetomidine 25 μg∕kg was intraperitoneally injected in group D+S, dexmedetomidine 25 μg∕kg and atipamezole 250 μg∕kg were intraperitoneally injected in group D+A+S, and atipamezole 250 μg∕kg was intraperitoneally injected in group A+S. Anesthesia was induced by inhaling 6% sevoflurane for 3 min starting from 60 min of monitoring and then maintained by inhaling 2. 1% sevoflurane for 1 h. The total duration, the number and average du- ration of epileptic waves were recorded during anesthesia. Blood samples were obtained from the left ventri-cle after the end of anesthesia for blood gas analysis. Rats were then sacrificed and blood samples were col-lected for measurement of the serum corticosterone concentration. Results No epileptic wave was found in group C. The serum concentration of corticosterone was significantly higher in the other four groups than in group C ( P＜0. 05). Compared with group S, the total duration of epileptic wave was significantly short-ened, the number of epileptic wave was reduced, and the concentration of corticosterone was decreased in group D+S (P＜0. 05), and no significant change was found in the total duration, the number and average duration of epileptic waves or serum concentration of corticosterone in D+A+S and A+S groups (P＞0. 05). Compared with group D+S, the total duration of epileptic wave was significantly prolonged, the number of epileptic wave was increased, and the serum concentration of corticosterone was increased in D+A+S and A+S groups (P＜0. 05). Conclusion Dexmedetomidine can inhibit the occurrence of cortical epileptiform EEG activity induced by sevoflurane anesthesia in the newborn rats, and the mechanism may be related to improving the hypothalamus-pituitary-adrenocortical axis hyperfunction mainly through activating the central 2-adrenoceptor.