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Objective:To evaluate the role of ketamine in postoperative cognitive dysfunction (POCD) and to clarify the association with subdiaphragmatic vagus nerve in mice.Methods:One hundred and forty-four SPF healthy male C57BL/6J mice, aged 18 months, weighing 32-35 g, were divided into 8 groups ( n=18 each) using a random number table method: sham operation group (group C), surgery group (group S), ketamine + surgery group (group SK), ketamine + surgery + subdiaphragmatic vagotomy group (group SK+ SDV), pseudo germ-free mice+ normal saline group (group GM+ V), pseudo germ-free mice that received fecal microbiota transplantation (FMT) from group S mice group (group GM+ S), pseudo germ-free mice that received FMT from group SK mice group (group GM+ SK), and pseudo germ-free mice received subdiaphragmatic vagotomy and FMT from group SK mice group (group GM+ SDV+ SK). Tibial fracture internal fixation was performed under anesthesia with 2.0% isoflurane. Ketamine 50 mg/kg was intraoperatively administered at the beginning of the suture in group SK. The fecal samples were collected at 24 h after surgery to prepare fecal bacteria filtrate in S and SK groups. The dorsal and ventral branches of subdiaphragmatic vagus nerve were cut prior to ketamine administration in SK+ SDV group and prior to FMT in GM+ SDV+ SK group. Broad-spectrum antibiotics dissolved in drinking water were given ad libitum to mice for 14 consecutive days at 2 weeks before FMT or subdiaphragmatic vagotomy and replaced once every 2 days to establish the pseudo germ-free model. Pseudo germ-free mice were gavaged with normal saline or fecal suspension 200 μl obtained from mice for 14 consecutive days at fixed time starting from 14 days after antibiotic intervention in GM+ SK and GM+ SDV+ SK groups. While normal saline was given instead for 14 consecutive days in GM+ V group. The fecal samples were collected after tibial fracture internal fixation or at 24 h after completion of FMT for 16S rRNA gene sequence analysis. The contents of interleukin-6 (IL-6), IL-17, tumor necrosis factor-alpha (TNF-α), IL-4 and IL-10 in the hippocampus were measured by enzyme linked-immuno-sorbent assay at 24 h after surgery or FMT. The spatial memory and learning ability was assessed by the Morris water maze test at 24 h after surgery or FMT. Results:Compared with group Sham, Simpson′s diversity index, Shannon index and Ace index were significantly decreased, the contents of IL-6, IL-17 and TNF-α were increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group S ( P<0.05). Compared with group S, Simpson′s diversity index, Shannon index and Ace index were significantly increased, the contents of IL-6, IL-17 and TNF-α were decreased, contents of IL-4 and IL-10 were increased, the escape latency in the training and testing phases and swimming distance were shortened, and the time spent in the target quadrant was prolonged in group SK ( P<0.05). Compared with group SK, Simpson′s diversity index, Shannon index and Ace index were significantly decreased, the contents of IL-6, IL-17 and TNF-α were increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group SK+ SDV ( P<0.05). Compared with group GM+ V, the contents of IL-6, IL-17 and TNF-α were significantly increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group GM+ S ( P<0.05). Compared with group GM+ S, the contents of IL-6, IL-17 and TNF-α were significantly decreased, contents of IL-4 and IL-10 were increased, the escape latency in the training and testing phases and swimming distance were shortened, and the time spent in the target quadrant was prolonged in group GM+ S ( P<0.05). Compared with group GM+ SK, the contents of IL-6, IL-17 and TNF-α were significantly increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group GM+ SDV+ SK ( P<0.05). Conclusions:Ketamine can improve intestinal flora disorders and reduce POCD in mice, and the mechanism may be related to subdiaphragmatic vagal nerve conduction.
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Objective:To evaluate the effects of intraoperative fluid therapy guided by different stroke volume variation (SVV)s on bleeding during laparoscopic hepatolobectomy and postoperative renal function.Methods:A total of 135 American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients of both sexes, aged 25-64 yr, scheduled for elective laparoscopic hepatolobectomy under general anesthesia, were divided into 3 groups ( n=45 each) using a random number table method: low SVV group (group L), medium SVV group (group M) and high SVV group (group H). In group L, group M and group H, SVVs were maintained at 10%-15%, 16%-20% and more than 21%, respectively.Before surgery and at 1, 3 and 5 days after the surgery, blood samples from the peripheral vein were taken for determination of serum blood urea nitrogen, creatinine and procalcitonin (PCT) concentrations.The occurrence of conversion to laparotomy, intraoperative volume of blood loss, volume of blood transfused, urine volume, operation duration, length of hospital stay and time to first flatus were recorded.On admission to the operating room (T 0), at skin incision (T 1), at the beginning of resection of the liver (T 2), after resection of the lobes of the liver (T 3) and at the end of the surgery (T 4), mean arterial pressure (MAP), heart rate (HR) and lactic acid (Lac) were recorded.The consumption of intraoperative norepinephrine, hypotension, arrhythmia and postoperative adverse reactions were recorded. Results:Compared with group L, the intraoperative volume of blood loss and consumption of intraoperative norepinephrine in group M and intraoperative volume of blood loss, the total amount of fluid infused and urine volume in group H were significantly decreased, consumption of furosemide and nitroglycerin in group H and the total amount of red blood cells infused in M and H groups were increased, length of hospital stay and time to first flatus in group M were shortened, concentration of serum PCT at 1 day after surgery was decreased in group M, MAP at T 3, 4 was increased in group M, and Lac at T 2-4 was increased in group H ( P<0.05). Compared with group M, the intraoperative volume of blood loss, consumption of intraoperative norepinephrine and consumption of furosemide and nitroglycerin were significantly increased, the total amount of fluid infused and urine volume were decreased, length of hospital stay and time to first flatus in group M were prolonged, concentration of serum PCT at 1 day after surgery was increased, MAP at T 3, 4 was decreased in group M, and Lac at T 2-4 was increased in group H ( P<0.05). There was no significant difference in the incidence of postoperative adverse reactions and intraoperative hypotension and arrhythmia among the 3 groups ( P>0.05). Conclusion:Intraoperative fluid therapy guided by SVV at 16%-20% during laparoscopic hepatolobectomy can decrease the intraoperative volume of blood loss and has less effect on renal function, which is helpful for postoperative outcomes.
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Objective:To evaluate the efficacy of acupuncture-drug balanced anesthesia in improving the outcomes following radical correction of tetralogy of Fallot (TOF) under cardiopulmonary bypass (CPB) in the pediatric patients.Methods:A total of 100 pediatric patients, aged 3-8 yr, weighing 9-24 kg, with American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective radical correction of TOF with CPB, were divided into 2 groups ( n=50 each) using a random number table method: acupuncture-drug balanced anesthesia group (group ADBA) and conventional anesthesia group (group CA). In group ADBA, transcutaneous acupoint electrical stimulation (disperse-dense wave, frequency 2/100 Hz, current intensity 6 mA, pulse width 0.2-0.6 ms) of Baihui (GV20) and bilateral acupoints of Neiguan (PC6), Hegu (LI4), and Ximen (PC4) acupoints was performed after induction of general anesthesia and maintained until the end of surgery.In group CA, the children received combined intravenous-inhalational anesthesia, and electrodes were only applied on the same acupoints without electrical stimulation.Venous blood samples were collected for blood routine examination and for determination of the concentrations of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha(TNF-α) at 30 min before surgery (T 1), 30 min after the start of surgery (T 2) and 1 h and 1, 2, 3 and 5 days after surgery (T 3-7). The length of hospital stay and development of postoperative major adverse events were recorded. Results:Compared with group CA, the plasma concentrations of IL-6, IL-8 and TNF-α at T 2-7 and white blood cell count, neutrophil count and neutrophil percentage at T 4-7 were significantly decreased, postoperative length of hospital stay was shortened ( P<0.05), and the incidence of acute lung injury was decreased obviously in group ADBA ( P<0.05). Conclusion:Acupuncture-drug balanced anesthesia can improve the outcomes following radical correction of TOF under CPB to a certain extent, and the mechanism is related to inhibiting inflammatory responses in pediatric patients.
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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.
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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.
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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.