Objective:To investigate the neuroprotective effect of long-term prophylactic use of buphthalein on mice with permanent distal middle cerebral artery occlusion and its relationship with the nuclear factor erysid 2 related factor 2 (Nrf2) pathway.Methods:Nrf2 + /+ wild-type and Nrf2 -/- knockout mice were randomly divided into control group (equal volume vegetable oil), low-dose butylphthalide group (20 mg/kg) and high-dose butylphthalide group (60 mg/kg), with 6 mice in each group. The drug was administered once a day by gavage for 1 month, and then a permanent middle cerebral artery occlusion model was induced by electrocoagulation. After the model was made, the drug was continued and the mice were sacrificed on the 10 th day. The modified Longa grading scale and the rotating rod test were used to evaluate neurological deficits on the 3 rd and 10 th day after the model was made. After the mice were sacrificed, the cerebral infarct volume was measured by triphenyltetrazolium chloride staining. The brain water content was measured by dry and wet weight method. The expression of Nrf2 pathway related factors, including Nrf2, heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) were measured by quantitative real-time PCR and Western blotting. Results:On the 10 th day after modeling, compared with the Nrf2 -/- control group, the neurological deficit was significantly milder, the volume of cerebral infarction and brain water content were significantly smaller, and the mRNA and protein levels of Nrf2, HO-1 and NQO1 were significantly higher in the Nrf2 + /+ control group, and the differences were statistically significant ( P<0.05). For Nrf2 + /+ mice, compared with the control group, the cerebral infarct volume was significantly reduced ( P<0.05), the brain water content was significantly reduced ( P<0.05), and the neurological function recovery was significantly better ( P<0.05), and the levels of Nrf2, HO-1, and NQO1 mRNA and protein were significantly higher in the high-dose butylphthalide group (all P<0.05). For Nrf2 -/- mice, there were no significant differences in neurological function, cerebral infarction group volume, brain water content, Nrf2, HO-1, NQO1 mRNA and protein levels among the groups. Conclusion:Long-term butylphthalide pretreatment can significantly improve the neurological function, reduce cerebral infarction volume, reduce brain water content, and increase Nrf2, HO-1, NQO1 mRNA and protein expression levels in mice with permanent distal middle cerebral artery occlusion, suggesting butylphthalide may play a neuroprotective effect by up-regulating the expression of Nrf2 gene and its downstream antioxidant stress factors HO-1 and NQO1.

Objective:To investigate the relationship between autophagy and nuclear factor E2 related factor 2(Nrf2) signaling pathway during high glucose-induced damage to Schwann cells.Methods:RSC96 were cells cultured in vitro and seeded in 96-well plates (1×10 4 cells/ml, 200 μl/well) or in 6-well plates (1×10 6 cells/ml, 2 ml/well) for 48 h. The cells were divided into 3 groups ( n=25 each) using a random number table method: control group (group C), high glucose group (group H) and high glucose+ autophagy agonist rapamycin group ( group H+ RAP). The cells were cultured in the common culture medium in group C. In group H, 50 mmol/L of glucose was added to the culture medium.In group H+ RAP, 50 mmol/L of glucose and 5 μmol/L rapamycin were added to the culture medium.At 48 h of incubation, the growth of cells was observed with inverted phase contrast microscope, the cell viability was measured using MTT method, apoptosis rate was determined by flow cytometry, malondialdehyde (MDA) content was determined by thiobarbituric acid method, superoxide dismutase (SOD) activity was detected using xanthine oxidase method, and the expression of Nrf2, P62 and microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) was determined by Western blot. Results:Compared with group C, the cell viability and SOD activity were significantly decreased, apoptotic rate and MDA content were increased, and expression of Nrf2, P62 and LC3Ⅱ was up-regulated in group H and group H+ RAP ( P<0.05). Compared with group H, the cell viability and SOD activity were significantly increased, apoptosis rate and MDA content were decreased, the expression of Nrf2 and LCII was up-regulated and P62 expression was down-regulated in group H+ RAP ( P<0.05). Conclusion:Enhanced autophagy can activate Nrf2 signaling pathway, which is the endogenous protective mechanism of Schwann cell injury induced by high glucose.

Peripheral nerve injury (PNI) is an important clinical complication, which brings long-term physical and psychological pain and economic burden to patients. There is no satisfactory treatment plan for PNI. Although microsurgery technology has been greatly developed, some peripheral nerve defects or ruptures caused by external forces can be repaired by surgery or nerve transplantation. However, due to the weak ability of nerve cell regeneration and surgical operations may cause damage to the injured nerves, the patient's functional recovery may not be able to achieve the desired effect. Therefore, it is urgent to find a safe and effective method to treat PNI. Mesenchymal stem cells have special differentiation potential and can differentiate into a variety of cell types in vitro and in vivo, and have received widespread attention from researchers. In this paper, the research progress of mesenchymal stem cells in nerve injury repair was summarized, and the characteristics, functions of mesenchymal stem cells and the mechanism of action in peripheral nerve injury repair were reviewed.

Objective:To evaluate the lung protection of pressure-controlled ventilation volume guaranteed (PCV-VG) in elderly patients undergoing laparoscopic surgery in Trendelenburg position.Methods:Sixty patients of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, aged 65-80 yr, with body mass index of 19-27 kg/m 2, scheduled for elective laparoscopic radical prostatectomy or laparoscopic radical cystectomy, were allocated into 2 groups ( n=30 each) by a random number table method: VCV group (group V) and PCV-VG group (group P). Tracheal intubation was performed after induction of anesthesia.The anesthesia machine was connected to perform mechanical ventilation with tidal volume of 7 ml/kg (corrected body weight), positive end-expiratory pressure at 5 cmH 2O, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 50%, fresh gas flow at 2 L/min and respiratory rate 12-15 breaths/min in two groups.Recruitment maneuver was performed with a pressure of 30 cmH 2O, lasting for 30 s, starting from 5 min before the end of administration.The airway peak pressure (P peak), airway plateau pressure (P plat), driving pressure (DP), and dynamic lung compliance (Cdyn) were measured at 5 min after intubation (T 1), 5 min after changing position (T 2), 5, 30, 60, 90 and 120 min of pneumoperitoneum (T 3-7) and 5 min after restoring the supine position and after the end of pneumoperitoneum (T 8). Blood samples were collected from the radial artery for blood gas analysis at T 1, T 4 and T 6 and when modified Aldrete score reached 10 in postanesthesia care unit, and pH value, partial pressure of arterial oxygen (PaO 2), partial pressure of arterial carbon dioxide (PaCO 2), arterial oxygen saturation (SaO 2) and alveolar-arterial oxygen gradient (P A-aO 2) were recorded.Blood samples were collected from the radial artery before induction of anesthesia and at the end of surgery for determination of concentrations of Clara cell protein (CC-16), interleukin-6 (IL-6) and neutrophil elastase (NE) in serum by enzyme-linked immunosorbent assay.The development of pulmonary complications was recorded within 7 days after surgery. Results:Compared with group V, P peak was significantly decreased at T 1-8, P plat and DP were decreased at T 5-7, Cdyn was increased at T 2-7, P A-aO 2 was decreased at T 1, 4, 6, serum CC-16, IL-6 and NE concentrations were decreased at the end of surgery ( P<0.05), and no significant change was found in the incidence of pulmonary complications within 7 days after surgery in group P ( P>0.05). Conclusion:PCV-VG can produce lung protection to some extent in elderly patients undergoing laparoscopic surgery in Trendelenburg position.

Objective To determine the median effective dose (EDs0) of etomidate inducing electroencephalogram (EEG) burst suppression (BS) in the patients with non-intracranial diseases.Methods American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 18-64 yr,with body mass index of 19-27 kg/m2,scheduled for elective non-intracranial surgery,were enrolled in this study.ED50 of etomidate was determined by Dixon's up-and-down sequential method.Etomidate was intravenously injected for 30 s at an initial dose of 0.30 mg/kg.The BS ratio was recorded within 6 min following the end of injection.Each time ED50 increased/decreased in the next patient depending on whether or not BS occurred.The difference between the two successive doses was 0.05 mg/kg.Successful induction of BS was defined as BS ratio＞ 10％,lasting more than 1 min.Probit analysis was used to calculate the ED50 and 95％ confidence interval of etomidate inducing EEG BS in the patients with non-intracranial diseases.Results The ED50 of etomidate inducing EEG BS was 0.70 mg/kg,and the 95％ confidence interval was 0.65-0.81 mg/kg in the patients with non-intracranial diseases.Conclusion The ED50 of etomidate inducing EEG BS is 0.70 mg/kg in the patients with non-intracranial diseases.

Objective To investigate the expression of microRNA-34a (miR-34a) and silent information regulator 1 (SIRT1) in human lens epithelial cells under H2O2-induced oxidative stress.Methods Different concentrations of H2O2 (0 μmol · L-1,100 μ mol· L-1,200 μmol · L-1,300 μmol · L-1,and 400 μmol · L-1) were used to stimulate SRA01/04 cells for 24 hours.Cell viability was measured using cell counting kit-8 (CCK-8) assay.Cell apoptosis was detected by flow cytometry.Expression levels of miR-34a/SIRT1 were measured by RT-PCR.Results CCK-8 assay showed that a certain concentration range of H2O2 had a proliferation inhibition on SRA01/04 cells.There was a dose response relationship between 100 μmol · L-1 and 400 μmol · L-1.Compared with 0 μmol · L-1 H2O2 group,the difference was statistically significant (all P ＜ 0.01).According to flow cytometry results,apoptotic rate of SRA01/04 cells in control group and H2O2(100-300 μmol · L-1) groups were (6.1 ± 1.2)％,(26.3 ± 1.8)％,(32.5 ± 2.2) ％,and (64.7 ± 5.3) ％.Compared with 0 μmol · L-1 H2 O2 group,the differences were statistically significant (all P ＜ 0.01).RT-PCR test results showed that the expression of miR-34a increased significantly in a dose-dependent manner after the SRA01/04 cells treated with different concentrations of H2O2,while SIRT1 expression level was decreased,there were significant differences compared with control group (all P ＜ 0.001).Conclusion There is a significantly increase of miR-34a and decrease of SIRT1 in human lens epithelial cells under the oxidative stress of a certain concentration of H2O2.Down-regulated expression of miR-34a can increase the survival rate of human lens epithelial cells under H2O2-induced oxidative stress.

Objective To evaluate the clinical value of continuous monitoring of intracranial pressure in old patients with hypertensive cerebral hemorrhage?Methods The clinical data of 217 cases of old patients with hypertensive cerebral hemorrhage, including 105 patients underwent continuous monitoring of intracranial pressure(monitoring group) and 112 patients without monitoring of intracranial pressure(control group),were retrospectively analyzed?The times and the total dosage of mannitol, the complications and prognosis of two groups were compared?Results The times and the total dosage of mannitol of monitoring group was respectively (42?1±5?4) times and ( 820?1±114?8) g,significantly less than that of control group((59?5±8?2) times, (1187?7±241?5) g;P=0?032,0?011)?The rate of pulmonary infection and stress ulcer showed no significant difference between two groups ( P = 0?608, 0?471 )?The rate of acute renal insufficiency and electrolyte disturbances was significantly lower in the monitoring group than that in the control group ( 11?4%( 12/104 ) vs?29?6%( 33/112 ) , 28?6%( 30/105 ) vs?41?9%( 47/112 );P = 0?004, 0?036 )?The prognosis of the monitoring group was better than that of the control group(72% vs?48%;χ2=13?02,P<0?01)?Conclusion Intracranial pressure monitoring has an important value for the treatment of old patients with hypertensive cerebral hemorrhage.

Objective To determine the median effective concentration (EC50) of lidocaine for obturator nerve block (ONB) guided by a nerve stimulator in patients undergoing transurethral resection of bladder tumor (TURBT).Methods American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients with bladder tumor,scheduled for elective TURBT,required ONB according to the results of cystoscopy or CT examination performed before operation,with body mass index of 19-30 kg/m2,aged 18-64 yr,were enrolled in the study.ONB was performed with lidocaine using the suprainguinal approach under the guidance of a nerve stimulator.The concentration of lidocaine was determined by up-and-down sequential trial.The initial concentration of lidocaine was 1.5％,and the ratio between the two successive concentrations was 1.2.Successful ONB was considered to be positive response.The EC50 and 95％ confidence interval of lidocaine for ONB guided by a nerve stimulator was calculated.Results The EC50 of lidocaine was 0.57％,and the 95％ confidence interval was 0.55％-0.59％ when used for ONB guided by a nerve stimulator.Conclusion The EC50 of lidocaine is 0.57％ when used for ONB guided by a nerve stimulator in the patients undergoing TURBT.

Objective To evaluate development of gastro-esophageal reflux (GER) during laparoscopic surgery in lateral jack-knife position under general anesthesia through comparing with reverse Trendelenburg/ Trendelenburg position in the patients lying supine.Methods Ninety patients of both sexes,aged 18-64 yr,of ASA physical status Ⅰ or Ⅱ,with body mass index of 18-30 kg/m2,scheduled for elective laparoscopic surgery under general anesthesia,were randomly divided into 3 groups (n =30 each):lateral jack-knife position group (group L),Trendelenburg position group (group T) and reverse Trendelenburg position group (group Tre).Anesthesia was induced with midazolam,sufentanil,propofol and cisatracurium besylate and maintained with propofol and remifentanil given by target-controlled infusion.A pH-sensitive probe was inserted through nose into the lower esophagus and pH value was continuously recorded until 1 min after extubation.GER was defined as pH value ≤ 4 lasting for ≥ 1 min in the lower esophagus during surgery.The development of GER during surgery and the lowest pH value in the lower esophagus when GER developed were recorded.Results Compared with group Tre,the incidence of GER (27％) and total number of times GER had occurred were significantly increased in group L,and no significant changes were found in the indices mentioned above in L and T groups.When GER developed,the lowest pH value in the lower esophagus was 2.1 ± 1.3,2.6 ± 1.2 and 3.5 in L,T and Tre groups,respectively.Conclusion The incidence of GER is 27 ％ during laparoscopic surgery when the patients are in lateral jack-knife position and it is higher than that obtained with reverse Trendelenburg position in the patients lying supine.

Objective To determine the median effective effect-site concentration (EC50 ) of remifentanil inhibiting responses to laryngeal mask airway insertion when combined with propofol in elderly male patients . Methods Thirty ASA physical status Ⅰ or Ⅱ male patients ,aged 65>yr ,with body mass index <30 kg/m2 , scheduled for elective transurethral resection of bladder tumor or prostate under general anesthesia ,were enrolled in this study .Anesthesia was induced with target-controlled infusion of propofol with a target plasma concentration (Cp) of 3 μg/ml .When Observer′s Assessment of Alertness/Sedation (OAA/S ) score ≤1 ,remifentanil target-controlled infusion was started with the initial target Cp set at 4.0 ng/ml . The concentration of propofol was adjusted until BIS value reached 55-65 ,and then the laryngeal mask airway was inserted .Modified Dixon’s up-and-down method was used to determine the Cp of remifentanil . Each time the Cp of remifentanil increased/decreased in the next patient depending on whether or not the response to laryngeal mask airway insertion occurred . The ratio of the two successive Cps was 1.2 .The response to laryngeal mask airway insertion was defined as development of coughing ,laryngospasm and/or body movement during insertion or within 3 min after insertion .The number of patients in whom inhibition of responses to insertion was effective/ineffective was recorded .The EC50 of remifentanil required to inhibit responses to laryngeal mask airway insertion and the 95% confidence interval when combined with propofol were calculated .Results The EC50 (95% confidence interval ) of remifentanil required to inhibit responses to laryngeal mask airway insertion was 1.86 (1.64-2.12) ng/ml when combined with propofol in elderly male patients .Conclusion The EC50 of remifentanil required to inhibit responses to laryngeal mask airway insertion is 1.86 ng/ml when combined with propofol in elderly male patients .