Objective To investigate the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in rotenone-mediated dopaminergic cell damage. Methods Neuronal rat adrenal pheochromecytoma(PC12) cells treated with rotenone were used as the cell model of Parkinson' s disease (PD). Cell viability of PC12 cells after exposure to rotenone was detected by MTT (methyl thiazolyl tetrazolium) method. Immanohistechemistry was used to detect the phosphorylation of ERK1/2 in cells exposed to rotenone. Western blotting was used to verify the phosphorylation of ERK1/2 and to observe the effect of PD98059, an inhibitor of the upstream mitogen activated protein kinase kinase (MEK) that phosphorylates and activates ERK1/2, on rotenone-induced ERK1/2 phosphorylation and cell viability.Results The viability (represented by A570 of PC12 cells exposed to 5 μmoL/L rotenone) declined with the increase of exposure time from 1 h to 24 h (%, 1 h :75.46±5.47, 2 h : 70.42±1.94, 4 h : 65.23± 0.96, 8 h : 59.04 ± 2.85, 24 h :29.64 ± 1.63, comparison between different time points(F=143.014, P=0.000) ; compared with control groups(100.00±2.89), q value: 17.07, 20.58, 24. 19, 28.50, 48.95 respectively, all P <0.01). After exposure to rotenone, phosphorylated ERK1/2 aggregated in the PC12 cells. Western blotting indicated that rotenone induced a biphasic phosphorylation of ERK1/2, which increased from 30 min after rotenone treatment, reached the peak at 1-2 h, decreased at 4 h, and increased again at 8 h, and disappeared after 16 h; PD98059 significantly inhibited ERK1/2 phosphorylation induced by rotenone, and attenuated cell injury examined at 1, 2 and 8 h. Conclusions Our study suggested that ERK1/2 activation plays a detrimental role in rotenone toxicity, and raised the possibility that abnormal patterns of ERK1/2 activation may contribute to dopaminergic neuronal cell death in PD.

Objective To investigate the effects of different values of PEEP on cardiac index (CI), stroke volume variation (SVV) and oxygen transport index (DO2I) in patients monitored by FloTrac/Vigileo system, and to provide some references for the hemodynamic management and improvement of oxygenation for patients. Methods Sixty patients scheduled for elective television (TV) auxiliary thoracoscope radical operation for esophageal cancer were included in this study. Data of CI, SVV and DO2I were observed by the FloTrac/Vigileo system. Changes of CI, SVV and DO2I were recorded after anesthesia induction and turn left side (T0), artificial pneumothorax with 0 PEEP after 5 minutes (T1), artificial pneumothorax with 5 PEEP after 5 minutes (T2), artificial pneumothorax with 10 PEEP after 5 minutes (T3), and artificial pneumothorax with 15 PEEP after 5 minutes (T4). Results Compared with T0, CI decreased and SVV increased significantly at T1, T2, T3 and T4(P<0.05). Compared with T1, CI decreased and SVV increased at T4. DO2I increased at T2 and T3 compared with that of T1(P<0.05). Conclusion PEEP may have a certain influence on CI and SVV in the process of operation. The values of 5-10 PEEP can significantly improve oxygenation and have a less influence on hemodynamics, which can be appropriately used in clinical care.

Objective To investigate the influence of different respiratory parameter setting during gynecological laparoscopic surgery on early postoperative cognitive function.Methods Eighty patients undergoing elective ovarian cancer or cervical cancer were grouped randomly into groups A, B,C and D.In group A patients were ventilated with respiratory parameters of VT 8 ml/kg,RR 12 times/min.While patients in groups B,C and D with identical minute volume 105 ml/kg though with respective RR of 12,1 5 and 18 times/min respectively.Patients in four groups were all graded by the MMSE at time points of preoperation(T0 ),postoperative 1 h(T1 ),6 h(T2 ),24 h(T3 ),48 h(T4 ), 72 h(T5 ).PaCO2 of arterial blood gas were tested before pneumoperitoneum(Ta)and immediately af-ter pneumoperitoneum(Tb).Results PaCO2 at Tb was higher in each group than that at Ta(P <0.05).Patients in group A showed the highest PaCO2 at Tb while PaCO2 in group C were lowest. The MMSE scores in group C were significantly higher than those in other groups at T1-T3 (P <0.05).The values at T4 in group A were lower (P <0.05)than those in other groups.Values at T1-T4 in group A were lower than that at T0 (P <0.05).In groups B and D at T1-T3 MMSE scores were lower than those at T0 and patients in group C showed lower MMSE scores at T1 and T2 (P <0.05).Conclusion Early postoperative cognitive function can be improved by regulating intraoperative respiratory parameters properly and increasing minute volume adequately in gynecological laparoscopic surgery.

Objective To investigate the effect of remote ischemic preconditioning (RIPC) on the lung injury during one-lung ventilation (OLV) in the patients undergoing thoracic surgery.Methods Eighty patients scheduled for elective radical operation for esophageal cancer,were randomly divided into 2 groups (n=40 each) using a random number table.control group (group C) and group RIPC.At 0 (T1),30 min (T2),1 h (T3) and 2 h (T4) of OLV,blood samples were obtained from the radial artery for blood gas analysis and determination of plasma concentrations of tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1ββ) and IL-10.Oxygenation index(OI),respiratory index(RI) and PaO2/PAO2 were calculated.Exhaled breath condensate was collected and the pH value was measured.Results Compared with group C,Oxygenation index was significantly increased,and respiratory index was decreased at T2-T4,the plasma concentrations of TNF-α and IL-1β were decreased,and the pH value of exhaled breath condensate was increased at T3-T4,and the plasma concentration of IL-10 was increased at T4 in group RIPC.Conclusion RIPC can inhibit inflammatory responses and reduce airway acidification,thus attenuating the lung injury during OLV in the patients undergoing thoracic surgery.

Objective To explore effects of Naikan cognitive therapy on improving clinical symptoms in patients with convalescent schizophrenia. Methods The 69 convalescent schizophrenic patients with convalescent clinical state were consecutively recruited. All the patients were divided into Naikan cognitive therapy ( NCT) group an control group at random and were pretreated with antipsychotic agent therapy. In NCT group,the patients received NCT for successive 7 days. In control group,the patients only received antipsychotic agent therapy. Pre-and post-treatment positive and negative syndrome scale( PANSS) , Nurses'observation scale for inpatient evaluation (NOSIE) were administered to all subjects. Results ① A significant decrease occurred in PANSS total score, negative symptom score, positive symptom score, compound scale score, general psychopathology score, reaction retardation score and paranoid score in NCT group ( t = 2. 672～7. 370, P < 0. 05). In the post-treatment, PANSS total score, negative symptom score, positive symptom score, compound scale score, reaction retardation score and thought disorder score were significantly lower in NCT group than those in control group ( t ' = 2. 696, P = 0. 009; t = 5. 186, P=0.000; t = 3.757, P = 0.001; t = 2.634,P = 0.011; t ' =2.376, P = 0.021). ②A significant decrease occurred in NOSIE total negative score( 10.43 ± 9. 24 vs 13. 87 ± 8. 03, t = 3. 463 , P = 0. 002) , irritation score(3. 13 ±0.43 vs8.53 ±4.98, t = 6. 139, P=0.000) and retardation score(1.07 ± 1.64 vs 2. 20 ±2.85, t = 2.067, P = 0.048) in NCT group. Conclusion NCT can possibly improve part clinical symptoms of patients with convalescent schizophrenia to a certain extent,especially negative symptom,but need to further prove the effect of NaiKan cognitive therapy.

Objective:To systematically review the efficacy and safety of dexmedetomidine and midazolam in procedural sedation. Methods: PubMed,EMBase,Cochrane Library,CNKI,CBM and WanFang databases were retrieved to collect the randomized controlled trials (RCT) about comparion of efficacy and safety between dexmedetomidine and midazolam in procedural sedation up to March, 2017. Based on the inclusion criteria, the data extraction and quality evaluation were performed, and then the systematic evaluation was carried out.The outcome measures for efficacy were the satisfaction scores and pain scores of the patients and clinicians;the outcome measures for safety comparison were hypotension, hypoxia, and circulatory and respiratory complications.Results:There were 14 RCT satisfied the inclusion criteria including 949 patients.Compared with midazolam group, the incidence of pain, delirium, and analgesia of the patients in dexmedetomidine group had significant differences (P<0.05);but the incidence of respiratory depression, low blood pressure had no significant differences (P>0.05).Conclusion:When the adult patients are sedated, dexmedetomidine can be used as an ideal alternative to midazolam sedation.

Objective To evaluate the effect of dexmedetomidine on the expression of Semaphorin 7A during lung ischemia-reperfusion (I/R) in rats.Methods Thirty healthy clean-grade adult male Sprague-Dawley rats,aged 8-12 weeks,weighing 200-240 g,were divided into 3 groups (n=10 each) using a random number table method:sham operation group (S group),I/R group and dexmedetomidine group (D group).Only sternotomy was performed,and the left hilum of lung was not clamped in S group.The model of lung I/R injury was established by clamping the left hilum of lung for 45 min followed by 120 min of reperfusion in I/R group.Dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before ischemia,and then the model was established in D group.The rats were sacrificed at the end of reperfusion,and the lungs were removed for examination of the pathological changes (using haematoxylin and eosin staining) which were scored and for determination of the wet to dry weight ratio (W/D ratio),expression of Semaphorin 7A protein and mRNA (by Western blot or real-time polymerase chain reaction),and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in lung tissues (by enzyme-linked immunosorbent assay).Results Compared with S group,W/D ratio and pathological scores were significantly increased,the expression of Semaphorin 7A protein and mRNA was up-regulated,and the contents of TNF-α and IL-1β were increased in I/R and D groups (P＜0.05).Compared with I/R group,W/D ratio and pathological scores were significantly decreased,the expression of Semaphorin 7A protein and mRNA was down-regulated,and the contents of TNF-α and IL-1 β were decreased in D group (P＜0.05).Conclusion The mechanism by which dexmedetomidine reduces lung I/R injury may be related to down-regulating Semaphorin 7A expression,thus inhibiting inflammatory responses of rats.

This study investigated the effect and mechanism of cell cycle reentry induced by 6-hydrodopamine (6-OHDA) in PCI2 cells.By using neural differentiated PCI2 cells treated with 6-OHDA,the apoptosis model of dopaminergic neurons was established.Cell viability was measured by MTT.Cell apoptosis and the distribution of cell cycle were assessed by flow cytometry.Western blot was used to detect the activation of extracellular regulator kinasel/2 (ERK1/2) pathway and the phosphorylation of retinoblastoma protein (RB).Our results showed that after PC12 cells were treated wtih 6-OHDA,the viability of PC12 cells was declined in a concentration-dependent manner.Flow cytometry revealed that 6-OHDA could increase the apoptosis ratio of PC12 cells in a time-dependent manner.The percentage of cells in G0/G1 phase of cell cycle was decreased and that in S phase and G2/M phase increased.Simultaneously,ERK1/2 pathway was activated and phos- phorylated RB increased.It was concluded that 6-OHDA could induce cell cycle reentry of dopa-minergic neurons through the activation of ERK1/2 pathway and RB phosphorylation.The aberrant cell cycle reentry contributes to the apoptosis of dopaminergic neurons.

Objective To systematically review the efficacy of dexmedetomidine mixed with ropivacaine for brachial plexus block in the patients undergoing upper limb surgery.Methods Medline,PubMed,Embase,Web of Science,Weipu,Wanfang,Zhiwang databases were searched for randomized controlled trials involving the efficacy of dexmedetomidine mixed with ropivacaine for brachial plexus block in patients undergoing upper limb surgery from the date of database establishment up to July 2017,and the trials were published in Chinese or in English.Evaluation indexes included onset time and duration of sensory and motor blocks and analgesia time when used for brachial plexus block.Trials were selected and data were extracted independently by 2 investigators,and meta-analysis was conducted using the Cochrane Collaboration's RevMan 5.3 software.Results Twelve randomized controlled trials were included in our metaanalysis.Compared with control group,the onset time of sensory and motor blocks was significantly shortened,the duration of sensory and motor blocks was prolonged,and analgesia time when used for brachial plexus block was prolonged in dexmedetomidine group (P＜0.01).Conclusion Dexmedetomidine mixed with ropivacaine can be effectively used for brachial plexus block in the patients undergoing upper limb surgery.

The hypoxia-inducible factor is a significant regulator of adaptive transcriptional response in hypoxia or hypoxia. Hypoxia-inducible factor (hypoXIA-inducible factor) loses its activity after hydroxylation by proline hydroxylase in a normoxic environment. Proline hydroxylase inhibitor is a kind of new small molecule oral preparation by inhibiting the proline hydroxylase, reducing the degradation of HIF, activating the hypoxia-induced way, adjusting including stimulates erythropoiesis, iron absorption and mobilization, angiogenesis, lipid, and glucose metabolism, inflammation, energy metabolism, cell growth and differentiation, and other physiological reaction, Showed more clinical benefits. In recent years, the application of proline hydroxylase inhibitors in the field of renal anemia has achieved apparent efficacy, and the research in the field of ischemic heart disease has also made significant progress in the future in the treatment of ischemic heart disease and other aspects of good application prospects.