Objective:To determine the median effective dose (ED 50) of esketamine for preoperative sedation in different aged pediatric patients. Methods:Pediatric patients, aged 1-6 yr, of American Society of Anaesthesiologists physical status Ⅰ, with the preoperative parental Separation Anxiety Scale (PSAS) score ≥3, undergoing elective surgery under general anesthesia, were selected.According to the age, the children were divided into 1 yr≤age<4 yr low-age group (group L) and 4 yr≤age< 6 yr high-age group (group H). Esketamine 0.5 mg/kg was intravenously injected in the first child in each group.The dose in the next child was determined according to PSAS scores, and the two consecutive dose gradient was 0.1 mg/kg; when the PSAS score in the previous child was ≥3, the dose in the next child was increased; when the PSAS score in the previous child was< 3, the dose in the next child was decreased until appearance of 7 turning points, and then the experiment was terminated.The ED 50 and 95% confidence interval of esketamine for preoperative sedation were calculated by probit analysis. Results:A total of 54 children were enrolled in this study, including 26 cases in group L and 28 cases in group H. The ED 50 and 95% confidence interval of esketamine were 0.413 (0.314-0.530) mg/kg and 0.282 (0.252-0.318) mg/kg in group L and group H, respectively.Compared with group L, ED 50 of esketamine was significantly decreased in group H ( P<0.05). Conclusions:The ED 50 of esketamine for preoperative sedation is 0.413 mg/kg in pediatric patients of 1 yr≤age<4 yr old and 0.282 mg/kg in those of 4 yr≤age<6 yr old, and the efficacy of esketamine for preoperative sedation increases with age.

Objective:To determine the potency of remimazolam in inhibiting ventilatory function during sedation in the patients undergoing internal jugular vein puncture.Methods:American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of either sex, aged 18-64 yr, with body mass index<30 kg/m 2, undergoing elective internal jugular vein puncture under local anesthesia, were enrolled in this study.Remimazolam was intravenously injected, and the dose was determined by up-and-down sequential allocation.The initial dose was 0.07 mg/kg and was increased/decreased in the next patient depending on whether the patients showed inhibition of ventilatory function, and the ratio between the 2 successive doses was 1.2.The criterion for inhibition of ventilatory function was defined as Integrated Pulmonary Index < 5.The median effective dose (ED 50) and 95% confidence interval of remimazolam in inhibiting ventilatory function were calculated by Dixon-Massey method. Results:Thirty-six patients were enrolled in this study.The ED 50 (95% confidence interval) was 0.106 (0.097-0.115) mg/kg. Conclusion:The ED 50 of remimazolam in inhibiting ventilatory function during sedation in internal jugular vein puncture is 0.106 mg/kg.

Objective To evaluate the effect of lidocaine on Ras homologue (Rho)/Rho kinase (ROCK) signaling pathway during endotoxin-induced lung injury (LI) in rats.Methods Forty SPF male Wistar rats,aged 5-8 weeks,weighing 200-250 g,were divided into 5 groups (n=8 each) using a random number table method:control group (group C),lipopolysaccharide (LPS) group (group LPS)and lidocaine at 3 different doses groups (L1-3 groups).LI was induced by intraperitoneal LPS 5 mg/kg (0.1 ml).The equal volume of normal saline was given intraperitoneally in group C.Lidocaine 2,4 and 8 mg/kg was intraperitoneally injected at 1 h before LPS administration in L1-3 groups,respectively.The animals were sacrificed at 6 h after LPS or normal saline administration.Broncho-alveolar lavage fluid (BALF) was collected for determination of concentrations of interleukin-1 beta (IL-1β),IL-6 and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay).The lung tissues were obtained for examination of the pathological changes which were scored and for measurement of the wet/dry weight ratio (W/D ratio) and activities of myeloperoxidase (MPO) and for determination of the expression of Rho,ROCK1,ROCK2,myosin phosphatase target protein 1 (MYPT1),phosphorylated MYPT1 (p-MYPT1)and ZO-1 (by Western blot).The phosphorylation of MYPT1 was calculated.Results Compared with group C,the activity of MPO,lung injury score,W/D ratio and concentrations of IL-1β,IL-6 and TNF-αin BALF were significantly increased,the expression of Rho,ROCK1 and ROCK2 was up-regulated,the phosphorylation of MYPT-1 was increased,and the expression of ZO-1 was down-regulated in the other four groups (P＜0.05).Compared with group LPS,the activity of MPO,lung injury score,W/D ratio and concentrations of IL-1β,IL-6 and TNF-α in BALF were significantly decreased,the expression of Rho,ROCK1 and ROCK2 was down-regulated,the phosphorylation of MYPT-1 was decreased,and the expression of ZO-1 was up-regulated in L1-L3 groups (P＜0.05).Conclusion Lidocaine can inhibit activation of Rho/ROCK signaling pathway during endotoxin-induced LI in rats,and the effect may be related to the antiinflammatory mechanism of lidocaine.

Objective To evaluate the relationship between the effect of peroxisome proliferator-activated receptor-γ (PPARγ) in pulmonary vascular remodeling and NADPH oxidase 4 (NOX-4) in rats with pulmonary hypertension.Methods Thirty-two healthy adult male Sprague-Dawley rats,aged 2 months,weighing 200-250 g,were divided into 4 groups (n =8 each) using a random number table method:control group (group C),pulmonary arterial hypertension group (group PH),PPARγ agonist rosiglitazone treatment group (group R),and PPARγ antagonist GW9662 treatment group (group G).In group PH,monocrotaline 60 mg/kg was injected subcutaneously in the neck and back to induce pulmonary hypertension.The suspension of rosiglitazone and normal saline 5 mg · kg-1 · d-1 and GW9662 solution 2 mg · kg-1 · d-1 were administered by intragastric gavage after injecting monocrotaline,in group R and group G,respectively,for 4 consecutive weeks.The mean pulmonary arterial pressure (mPAP) was measured at 4 weeks after establishing the model.The animals were then sacrificed,and the lungs were removed for microscopic examination of the pathological changes (with a light microscope) and for determination of the expression of PPARγ and NOX-4 protein and mRNA in lung tissues (by real-time polymerase chain reaction or Western blot).The percentage of media thickness of pulmonary arterioles was calculated.Results Compared with group C,the mPAP and percentage of media thickness of pulmonary arterioles were significantly increased,the expression of PPARγ protein and mRNA was down-regulated,and the expression of NOX-4 protein and mRNA was up-regulated in PH,R and G groups (P＜0.05).Compared with group PH,the mPAP and percentage of media thickness of pulmonary arterioles were significantly decreased,the expression of PPARγ protein and mRNA was up-regulated,and the expression of NOX-4 protein and mRNA was down-regulated in group R,and the mPAP and percentage of media thickness of pulmonary arterioles were significantly increased,the expression of PPARγ protein and mRNA was down-regulated,and the expression of NOX-4 protein and mRNA was up-regulated in group G (P＜0.05).Conclusion The mechanism of endogenous protective effect of PPARγ in the development of pulmonary hypertension and pulmonary vascular remodeling may be related to down-regulating the expression of NOX-4 in rats.

Objective To evaluate the effect of dexmedetomidine on high-mobility group box 1 protein (HMGB1)/Toll-like receptors (TLRs) signaling pathway during lung injury in septic rats.Methods Twenty-four SPF healthy adult male Wistar rats,aged 15-18 weeks,weighing 200-250 g,were divided into 3 groups (n =8 each) using a random number table:sham operation group (group S),sepsis group (group Sep) and dexmedetomidine group (group D).Dexmedetomidine 25 μg/kg was intraperitoneally injected in D group,while the equal volume of normal saline was given instead in S and Sep groups.Sepsis was produced by cecal ligation and puncture in Sep and D groups.The rats were sacrificed at 24 h after operation,and the right lung was removed for examination of the pathological changes which were scored and for determination of myeloperoxidase (MPO) activity,content of interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) in lung tissues (by enzyme-linked immunosorbent assay),wet to dry weight ratio (W/D ratio) and expression of HMGB1,TLR2 and TLR4 in lung tissues (by Western blot).Results Compared with group S,the MPO activity,lung injury score,W/D ratio,content of IL-1β,IL-6,TNF-α and expression of HMGB1,TLR2 and TLR4 were significantly increased in Sep and D groups (P＜0.05).Compared with group Sep,the MPO activity,lung injury score,W/D ratio,content of IL-1β,IL-6,TNF-α and expression of HMGB1,TLR2 and TLR4 were significantly decreased in group D (P＜0.05).Conclusion Dexmedetomidine reduces lung injury through inhibiting HMGB1/TLRs signaling pathway in septic rats.

Objective To evaluate the effect of dexmedetomidine on nerve regeneration following cerebral ischemia-reperfusion (Ⅰ/R) in mice and the role of transforming growth factor-beta 1 (TGF-β1) in brain tissues.Methods Sixty healthy SPF male C57BL/6J mice,weighing 23-25 g,aged 8-10 weeks,were divided into 5 groups (n =12 each) using a random number table method:sham operation group (group Sham),Ⅰ/R group,dexmedetomidine group (group D),dexmedetomidine plus IgG1 isotype control monoclonal antibody group (group DI) and dexmedetomidine plus TGF-β1 neutralizing monoclonal antibody group (group DA).Cerebral Ⅰ/R was induced by occlusion of the middle cerebral artery followed by reperfusion.Dexmedetomidine 50 μg/kg was intraperitoneally injected every 24 h for 14 days starting from 14 days of reperfusion in group D.TGF-β1 neutralizing monoclonal antibody 20 μg and IgG1 isotype control monoclonal antibody 20 μg were intraperitoneally injected at 30 min prior to dexmedetomidine injection in group DA and group DI,respectively.5-bromodeoxyuridine (BrdU) 100 mg/kg was intraperitoneally injected and injected again at an 8-h interval on 27 days of reperfusion.Forced swimming test (FST),sucrose consumption test (SCT) and open field test (OFT) were performed at 16 h after the second administration of BrdU.After the end of behavior testing,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone on ischemic side was measured by immunohistochemistry,and the expression of TGF-β1 protein and mRNA in brain tissues in ischemic area was detected using Western blot and real-time polymerase chain reaction,respectively.Results Compared with group Sham,the time spent floating in FST was significantly prolonged,the percent of time spent in the central region in OFT and sucrose solution intake in SCT were decreased,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone was increased,and the expression of TGF-β1 protein and mRNA was up-regulated in group Ⅰ/R (P＜0.05 or 0.01).Compared with group Ⅰ/R,the time spent floating in FST was significantly shortened,the percent of time spent in the central region in OFT and sucrose solution intake in SCT were increased,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone was increased,and the expression of TGF-β1 protein and mRNA was up-regulated in group D (P＜0.05 or 0.01).Compared with group D,the time spent floating in FST was significantly prolonged,the percent of time spent in the central region in OFT and sucrose solution intake in SCT were decreased,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone was decreased in group DA (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group DI (P＞0.05).Conclusion Dexmedetomidine can relieve depression and anxiety following cerebral Ⅰ/R,thus promotes nerve regeneration and the mechanism is related to up-regulating the expression of TGF-β1 in brain tissues of mice.

Objective To evaluate the effect of multimodal analgesia with diclofenac sodium on cognitive function following radical resection for colon cancer in elderly patients. Methods Sixty American Society of Anesthesiologists physical statusⅠorⅡpatients of either sex, aged 65-80 yr, weighing 45-85 kg, scheduled for elective open sigmoidectomy under general anesthesia, were divided into control group and test group by a random number table method with 30 patients in each group. In test group, diclofenac sodium suppository was administrated rectally before surgery and placed at about 2 to 3 cm above the anal dentate line, diclofenac sodium suppository 50 mg was given at 2 h before surgery and 4 h after surgery, followed by administration once every 12 h until 2 days after surgery. Patient-controlled intravenous analge-sia was performed after operation, dezocine 5 mg was intravenously injected when VAS score was more than 4 points within 48 h after surgery. The concentrations of serum interleukin-6 ( IL-6) , IL-8 and tumor nec-rosis factor-alpha ( TNF-α) were measured by enzyme-linked immunosorbent assay before surgery ( T0 ) and at 2, 6, 12, 24 and 48 h after surgery ( T1-5 ) . The postoperative requirement for rescue analgesia, post-operative analgesia satisfaction score, time of passing the first flatus and first postoperative off-bed time were recorded. Cognitive function was assessed at 1 day before surgery and 7 days after surgery, and the occur-rence of postoperative cognitive dysfunction was recorded. Results Compared with control group, the ser-um concentrations of IL-6 at T2-5 , IL-8 at T1-5 and TNF-αat T2-4 were significantly decreased, the require-ment for rescue analgesia and incidence of postoperative cognitive dysfunction were decreased, and the timeof passing the first flatus and first postoperative off-bed time were shortened in test group ( P<0. 05) . Con-clusion Diclofenac sodium for multimodal analgesia can improve cognitive function following radical resec-tion for colon cancer in elderly patients.

Objective To analyze the independent risk factors and complications for perioperative hyperbilirubinemia in Stanford type A aortic dissection undergoing operation and investigate the management strategy of perioperative hyperbilirubi-nemia. Methods Between January 2013 and January 2018 from the department of great vessel surgery of heart centre of,290 cases of patients with Stanford type A aortic dissection undergoing operation were collected consecutively,male 210 cases,fe-male 80 cases. The related data and perioperative peak hyperbilirubinemia were recorded. According to the perioperative peak hyperbilirubinemia,patients were divided into 2 groups:≥51. 3 μmol/ L group and < 51. 3 μmol/ L group. Univariate and lo-gistic regression analysis were used to identify the independent risk factors. The perioperative complications were also recorded. Results Preoperative total bilirubin ≥ 17. 1 μmol/ L(OR = 2. 105,95％ CI: 1. 153 - 3. 125,P = 0. 016),cardiopulmonary bypass time > 3. 5 h(OR = 1. 103,95％ CI: 1. 316 - 6. 151,P = 0. 031),a large number of hemolysis(OR = 1. 503,95％CI: 1. 506 - 6. 651,P = 0. 029),the input amount of 24 h allogeneic red blood cell > 2000 ml(OR = 1. 381,95％ CI:0. 956 - 2. 552,P = 0. 036)were the independent risk factors for perioperative hyperbilirubinemia. The incidence rate of post-operative acute hepatic failure(2. 5％ vs. 0,P = 0. 021)and artificial liver therapy(2. 5％ vs. 0,P = 0. 021)in≥51. 3μmol/ L group were significantly increased. The incidence rate of postoperative acute lung injury(37. 5％ vs. 25. 2％,P =0. 039)and acute kidney injury(38. 7％ vs. 19. 5％,P = 0. 035)in 51. 3 μmol/ L group were also significantly increased. The duration of mechanical ventilation[(4. 1 ± 1. 6)days vs. (2. 8 ± 1. 3)days,P < 0. 05]and ICU stay time[(5. 1 ± 2. 3)days vs. (3. 9 ± 1. 8)days,P = 0. 035]and hospitalization time[( 19. 3 ± 3. 1)days vs. ( 17. 3 ± 2. 5)days,P = 0. 035]were sig-nificantly prolonged. Temporary nerve dysfunction(52. 5％ vs. 32. 6％,P = 0. 002)and in-hospital mortality( 17. 5％ vs. 8. 1％,P = 0. 037)were significantly increased. Conclusion Preoperative total bilirubin ≥ 17. 1 μmol/ L,cardiopulmonary bypass time > 3. 5 h,a large number of hemolysis,the input amount of 24 h allogeneic red blood cell > 2000 ml were the in-dependent risk factors for perioperative hyperbilirubinemia in Stanford type A aortic dissection. The perioperative complications in≥51. 3 μmol/ L group were significantly increased. Therefore,more attention should be paid to the independent risk factors for perioperative hyperbilirubinemia in Stanford type A aortic dissection,hyperbilirubinemia and its clearance should be moni-tored more actively and dynamically,the cause should be found more precisely,the treatment be more comprehensive to achieve to control the level of bilirubinemia and improve the prognosis.

Objective To explore the clinical effect of intranasal dexmedetomidine as premedication on sedation and analgesia during painless electronic colonoscopy in children, and to investigate its optimal dose. Methods Ninety children scheduled for painless electronic colonoscopy were divided into three groups by using a computer?generated randomization schedule, 30 per group. Children were pretreated with 0. 2 mg/kg midazolam ( group A) , 1. 0μg/kg dexmedetomidine ( group B) or 2. 0μg/kg dexmedetomidine ( group C) by nasal drip 30 min before operation. The anesthesia protocol was programmed by propofol in the three groups. After eyelash reflex disappeared, the examination was performed. Mean artery blood pressure ( MAP ) , heart rate (HR), respiratory rate (RR) and oxygen saturation (SPO2) of children were recorded at 10 min before intranasal administration ( T0 ) , 30 min after intranasal administration ( T1 ) , at the onset of eyelash reflex disappearance ( T2 ) and the onset of examination initiating( T3 ) , at lens passing through splenic flexure ( T4 ) , or through hepatic flexure ( T5 ) , at the end of examination ( T6 ) and when patients were fully awake ( T7 ) , respectively. Bispectral index ( BIS) and the observer's assessment of alertness/sedation scale ( OAA/S) were performed at 10 min before intranasal administration ( T0 ) , 10 min, 20 min and 30 min after intranasal administration in the three groups. Mood score at parent?children separation and venipuncture acceptance score were also recorded. The adverse reactions during examination were analyzed. The above observed indices were compared among the three groups. If there was statistical difference ( P<0. 05 ) , pairwise comparison was performed ( P<0. 017) . Results The children's haemodynamics were all stable in the three groups. Compared with group A and group B at the same time point, BIS and OAA/S were all lower ( P<0. 017) in 10 to 30 min after intranasal administration in group C. Compared with group A and group B, mood score at parent?children separation and venipuncture acceptance score were both higher ( P<0. 017) in group C. Compared with group A and B, anesthetic revival time and consumption of propofol were shorter or lower in group C (P<0. 017). Compared with group A and group B, the incidences of intraoperative adverse reactions including hypertension, sinus tachycardia, restless moving and postoperative restlessness were all lower in group C(P<0. 017). The rate of intranasal stimulus in group B and group C were both lower than that of group A( P<0. 017) . The rate of injection pain of group C was lower ( P<0. 017 ) than that of group A and B. Conclusion Intranasal administration of dexmedetomidine can be safely applied to children receiving painless electronic colonoscopy, and it can improve children's compliance effectively and yield to satisfactory anesthetic effect. Moreover, the administering efficacy of dexmedetomidine with the dose of 2. 0μg/kg was superior to 1. 0μg/kg.

Objective To evaluate the effect of hydrogen on the postoperative cognitive function in aged mice.Methods Sixty aged male Kunming mice,aged 12-14 months,weighing 35-45 g,were assigned into 3 groups (n=20 each) using a random number table:sham operation group (group Sham),partial hepatectomy group (group PH) and partial hepatectomy plus hydrogen-enriched saline group (group PH-H).On preoperative day 3,during operation and on postoperative day 3,hydrogen-enriched saline 10 ml/kg was intraperitoneally injected once a day in group PH-H,and the equal volume of normal saline was intraperitoneally injected once a day in S and PH groups.The spatial probe test was performed on postoperative day 7 to evaluate the cognitive function.Ten mice were selected on postoperative days 3 and 7 (after the end of the spatial probe test),and blood samples were collected for determination of serum tumor necrosis factor-alpha (TNF-α),interleukin-lbeta (IL-1β) and high-mobility group box 1 protein (HMGB1) concentrations by enzyme-linked immunosorbent assay.The animals were sacrificed after blood sampling,brains were removed and hippocampi were isolated for detection of the expression of TNF-α,IL-1β and HMGB1 by Western blot.Results Compared with group S,the percentage of time of staying at the target quadrant and the number of crossing the platform within 1 min were significantly decreased,the serum concentrations of TNF-α,IL-1β and HMGB1 were increased,and the expression of hippocampal TNF-α,IL-1β and HMGB1 was up-regulated in group PH (P＜0.05),and no significant change was found in the variables mentioned above in group PH-H (P＞0.05).Compared with group PH,the percentage of time of staying at the target quadrant and the number of crossing the platform within 1 min were significantly increased,the serum concentrations of TNF-α,IL-1β and HMGB1 were decreased,and the expression of hippocampal TNF-α,IL-1β and HMGB1 was down-regulated in group PH-H (P＜0.05).Conclusion Hydrogen can improve the postoperative cognitive function in aged inice.