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 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 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 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 evaluate the effect of ulinastatin on endoplasmic reticulum stress in car-diomyocytes of patients undergoing beating heart mitral valve replacement(MVR). Methods A total of 80 patients of both sexes with rheumatic heart disease complicated with mitral valve stenosis, aged 38-59 yr, weighing 43-73 kg, with American Society of Anesthesiology physical statusⅡorⅢ, scheduled for elective MVR, were divided into ulinastatin group(UTI group, n=40)and normal saline group(NS group, n=40) using a random number table. Immediately after opening the right atrium(T0), at 30 min of cardiopulmonary bypass(T1)and while suturing the right atrium(T2), blood samples from the radial artery were collected to determine the concentrations of plasma creatine kinase-MB and cardiac troponin T by enzyme-linked immu-nosorbent assay, and the right auricle specimens were collected for determination of the expression of glucose-regulated protein 78, CCAAT∕enhancer-binding protein homologous protein, c-Jun amino-terminal kinase (JNK)protein and mRNA(by real-time polymerase chain reaction or Western blot)and phosphorylated JNK (p-JNK)expression(by Western blot). The apoptosis in cardiomyocytes was detected by TUNEL at T0,2, and the apoptosis rate was calculated. Results Compared with group NS, the concentrations of plasma crea-tine kinase-MB and cardiac troponin T at T1,2and the apoptosis rate of cardiomyocytes were significantly de-creased at T2, and the expression of glucose-regulated protein 78, CCAAT∕enhancer-binding protein homolo-gous protein and JNK protein and mRNA and p-JNK was down-regulated at T1,2in group UTI(P<0.05). Conclusion The mechanism by which ulinastatin reduces myocardial damage is related to inhibiting endo-plasmic reticulum stress in cardiomyocytes of patients undergoing beating heart MVR.

Objective To evaluate the effect of multimodal warming regimen on the postoperative outcomes and cost-effectiveness in the patients undergoing resection of liver cancer.Methods Sixty Ameri-can Society of Anesthesiologists physical status ⅠorⅡ patients of both sexes, aged 35-64 yr, with body mass index of 18-24 kg∕m2, of liver function Child-Pugh grade A, scheduled for elective resection of liver cancer, were divided into 2 groups(n=30 each)using a random number table: routine warming group (group R)and multimodal warming group(group M). Quilts were covered on the body exposed before in-duction of anesthesia, and the abdominal cavity was washed with the room-temperature peritoneal lavage flu-id during operation in group R.In group M, the lower body was covered using the forced-air warming system at 30 min before induction of anesthesia, and the temperature was maintained at 38℃ until the end of oper-ation; the solution used for infusion was warmed to 42 ℃ using a fluid-warming device during operation;the abdominal cavity was washed with 0.9% sodium chloride injection which was prewarmed to 37℃ during operation.The rectal temperature was recorded after anesthesia induction and before tracheal intubation (T1), at 30, 60, 90, 120 and 150 min after anesthesia and at the end of operation(T2-7). The parame-ters of thrombelastogram were measured before induction of anesthesia(T0), at T7and at 12 h after opera-tion(T8).At T0, T7, T8and 24 and 48 h after operation(T9,10), blood samples were taken from the in-ternal jugular vein for determination of plasma interleukin-6 concentrations by enzyme-linked immunosorbent assay.The extubation time, duration of post-anesthesia care unit stay, intraoperative blood loss, blood transfusion, requirement for allogeneic blood transfusion, length of hospitalization, occurrence of postoper-ative shivering, occurrence of hypothermia, volume of drainage on 1st and 3rd days after operation, neu-trophil count, cost of general anesthesia and total cost of hospitalization were recorded.Results Compared with group R, the extubation time and duration of post-anesthesia care unit stay were significantly short-ened, the intraoperative blood loss, volume of blood transfused, and volume of drainage on 1st day after operation were reduced, length of hospitalization was shortened, the requirement for allogeneic blood trans-fusion and incidence of postoperative shivering and hypothermia were decreased, the body temperature was increased at T2-7, R and K were shortened at T7, α angle was enlarged, the neutrophil count on 1st day af-ter operation was reduced, the concentration of plasma interleukin-6 was decreased at T8and T9, the cost of anesthesia was increased, and the total cost of hospitalization was reduced in group M(P<0.05). Con-clusion Multimodal warming regimen can not only promote postoperative outcomes but also improve the cost-effectiveness in the patients undergoing resection of liver cancer.