OBJECTIVE: Phenolic acids widely exist in the human diet and exert beneficial effects such as improving glucose metabolism. It is not clear whether phenolic acids or their metabolites play a major role in vivo. In this study, caffeic acid (CA) and ferulic acid (FA), the two most ingested phenolic acids, and their glucuronic acid metabolites, caffeic-4'-O-glucuronide (CA4G) and ferulic-4'-O-glucuronide (FA4G), were investigated. METHODS: Three insulin resistance models in vitro were established by using TNF-α, insulin and palmitic acid (PA) in HepG2 cells, respectively. We compared the effects of FA, FA4G, CA and CA4G on glucose metabolism in these models by measuring the glucose consumption levels. The potential targets and related pathways were predicted by network pharmacology. Fluorescence quenching measurement was used to analyze the binding between the compounds and the predicted target. To investigate the binding mode, molecular docking was performed. Then, we performed membrane recruitment assays of the AKT pleckstrin homology (PH) domain with the help of the PH-GFP plasmid. AKT enzymatic activity was determined to compare the effects between the metabolites with their parent compounds. Finally, the downstream signaling pathway of AKT was investigated by Western blot analysis. RESULTS: The results showed that CA4G and FA4G were more potent than their parent compounds in increasing glucose consumption. AKT was predicted to be the key target of CA4G and FA4G by network pharmacology analysis. The fluorescence quenching test confirmed the more potent binding to AKT of the two metabolites compared to their parent compounds. The molecular docking results indicated that the carbonyl group in the glucuronic acid structure of CA4G and FA4G might bind to the PH domain of AKT at the key Arg-25 site. CA4G and FA4G inhibited the translocation of the AKT PH domain to the membrane, while increasing the activity of AKT. Western blot analysis demonstrated that the metabolites could increase the phosphorylation of AKT and downstream glycogen synthase kinase 3β in the AKT signaling pathway to increase glucose consumption. CONCLUSION In conclusion, our results suggested that the metabolites of phenolic acids, which contain glucuronic acid, are the key active substances and that they activate AKT by targeting the PH domain, thus improving glucose metabolism.

Objective:To evaluate the effect of sedation management based on visual analysis of electroencephalography (EEG) on postoperative delirium in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods:Eighty patients, aged ≥ 18 yr, of American Society of Anesthesiologists physical status Ⅲ or Ⅳ, with New York Heart Association Ⅱ-Ⅳ, scheduled for elective cardiac valve replacement with CPB, were randomly divided into visual analysis of EEG-guided sedation management group (group A, n=40) and BIS-guided sedation management group (group B, n=40). The target plasma concentration of propofol was adjusted to maintain the depth of anaesthesia at grade C or grade D in group A and BIS value at 40-60 in group B. Propofol consumption during CPB and total consumption of propofol during surgery, requirement for vasoactive agents during surgery, and parameters of intraoperative arterial blood gas analysis were recorded.Postoperative delirium was evaluated using Confusion Assessment Method for the Intensive Care Unit (ICU) at 1-7 days after surgery.Extubation time, length of ICU stay, length of postoperative hospital stay and intraoperative awareness were also recorded. Results:Compared with group B, the length of postoperative hospital stay was significantly shortened, the incidence of postoperative delirium was decreased, and no significant change was found in the parameters of arterial blood gas analysis, propofol consumption, requirement for vasoactive agents, extubation time, or length of postoperative ICU stay in group A ( P<0.05). No intraoperative awareness occurred in both groups. Conclusion:Sedation management based on visual analysis of EEG is helpful in decreasing the development of postoperative delirium in the patients undergoing cardiac valve replacement with CPB.

Objective: To evaluate the effect of anesthesia management based on regional cerebral oxygen saturation (rSO₂)-bispectral index (BIS)-goal-directed hemodynamic multi-modal monitoring on acute kidney injury (AKI) after cardiac valve replacement. Methods: A total of 238 patients of both sexes, aged 18-75 yr, weighing 45-95 kg, of American Society of Anesthesiologists physical status Ⅲ or Ⅳ (New York Heart Association class Ⅱ or Ⅲ ), undergoing elective cardiac valve replacement, were assigned into routine experience group (group C, n=122) and multi-mode monitoring group (group M, n=116) using a random number table method.After admission to the operating room, the invasive blood pressure of radial artery, central venous pressure, electrocardiogram, SpO₂ and end-tidal pressure of carbon dioxide were recorded in group C, and rSO₂, BIS, stroke volume variation, cardiac index and stroke volume index were monitored based on the monitoring in group C. The patients were tracheally intubated when BIS value was about 50.BIS value was maintained between 45 and 55, rSO₂ was maintained not less than 20% of the baseline value or the absolute value not less than 55%, and fluctuation in mean arterial pressure did not exceed 20% of the baseline value, and stroke volume index was maintained >25 ml/m² and cardiac index>2.5 L·min^-1 ·m^-2, maintaining not lower than the baseline value before induction in special conditions.The intraoperative volume of fluid infused, infusion of allogeneic blood, consumption of propofol, time of cardiopulmonary bypass, aortic cross-clamping time, anesthesia time, operation time, occurrence of AKI within 48 h after operation, renal replacement therapy, extubation time, duration of intensive care unit stay, postoperative length of hospital stay, development of other serious postoperative complications and fatality rate at day 30 after operation were recorded. Results: Compared with group C, the incidence of AKI was significantly decreased, the volume of plasma infused and consumption of propofol were reduced, the extubation time, duration of intensive care unit stay and postoperative length of hospital stay were shortened (P<0.05), and no significant change was found in the rate of renal replacement therapy, constituent ratio of AKI degree, incidence of other serious postoperative complications or mortality rate at day 30 after operation in group M (P>0.05). Conclusion Anesthesia management based on rSO₂-BIS-goal-directed hemodynamic multi-modal monitoring can decrease the occurrence of AKI after cardiac valve replacement.

Objective To explore the effect of sufentanil postconditioning on the focal cerebral is-chemia reperfusion injury in diabetic rats. Methods An intraperitoneal injection of 50 mg/kg streptozotocin was used to induce diabetes in rats. Meanwhile,the diabetes mellitus model was confirmed by the blood glu-cose level over 16. 7 mmol/L. The diabetes mellitus male SD rats,weighting 250-300 g,were randomly divid-ed into 3 groups:sufentanil postconditioning diabetic group (SP-DM),ischemia reperfusion diabetic group (IR-DM),sham operation diabetic group(sham-DM),with 12 in each group. The non-diabetic rats were randomly divided into 3 groups:sufentanil postconditioning non-diabetic group(SP-NDM), ischemia reperfu-sion non-diabetic group(IR-NDM),sham operation non-diabetic group(sham-NDM),with 12 in each group. All rats in the IR-NDM/DM group and SP-NDM/DM group were exposed to the right middle cerebral artery occlusion for 90 minutes followed by 24 hours reperfusion. The sufentanil 1 μg/kg were injected into the rats in SP-NDM/DM group via tail vein at 5 minutes before reperfusion. Normal saline was injected into the rats in sham-NDM/DM group and IR-NDM/DM group at 5 minutes before reperfusion. At 24 hours after reperfu- sion,the neurological deficit scores( NDS) were assessed,then all the rats were sacrificed. Infarct volume, which was determined by 2,3,5-triph-enyltetrazolium ( TTC) staining,and water content of right hemisphere for brain edema were also measured. Results All rats showed neurological deficit,brain infarction and brain edema after focal cerebral ischemia reperfusion. (1) At 24 hours after reperfusion,the neurological deficit score in IR-DM group(3. 4±0. 4) was significantly higher than that in the IR-NDM group(2. 8± 0. 5) ( t=2. 313,P<0. 05),there was no significant difference in neurological deficit score between the SP-DM group (3. 3±0. 4) and the IR-DM group(t=1. 546,P>0. 05). (2) At 24 hours after reperfusion,the infarct volume in IR-DM group((58. 3±2. 1)%) was significantly higher than that in the IR-NDM group((32. 1±2. 6)%) (t=2. 912, P<0. 05), there was no significant difference in infarct volume between the SP-DM group ((56. 9±2. 1)%) and the IR-DM group(( 58. 3 ± 2. 1)%) ( t=1. 633,P>0. 05). ( 3) At 24 hours after reperfusion,the water content of the right hemisphere in IR-DM group(( 89. 3± 3. 5)%) was significantly higher than that in the IR-NDM group((82. 6±3. 9)%)(t=2. 218,P<0. 05),there was no significant differ-ence in water content of the right hemisphere between the SP-DM group(( 87. 5±3. 4)%) and the IR-DM group(t=1. 730,P>0. 05). Conclusion Sufentanil postconditioning loses neuroprotection against focal cer-ebral ischemia reperfusion injury in diabetic rats.

Objective To evaluate the effect of dexmedetomidine on postoperative outcomes in pa-tients undergoing off-pump coronary artery bypass grafting ( OPCABG) . Methods One hundred and twen-ty-two patients of both sexes, aged 40-75 yr, with body mass index of 18. 5-32. 0 kg∕m2 , of American So-ciety of Anesthesiologists physical status Ⅲ or Ⅳ, with New York Heart Association Ⅱ or Ⅲ, with lelf ventricular ejection fraction>40％, scheduled for elective OPCABG, were divided into 2 groups ( n=61 each) using a random number table method: dexmedetomidine group ( group D) and control group ( group C) . Dexmedetomidine was intravenously infused in a loading dose of 0. 6μg∕kg at 15 min before anesthesia induction, followed by a continuous infusion of 0. 4 μg · kg-1 · h-1 until the end of surgical procedure in group D. The equal volume of normal saline was given instead in group C. The emergence time, extubation time, length of intensive care unit stay and postoperative length of hospital stay were also recorded. Results Compared with group C, the extubation time, length of intensive care unit stay, and postoperative length of hospital stay were significantly shortened, and the emergence time was prolonged in group D ( P<0. 05) . Conclusion Dexmedetomidine can promote postoperative outcomes in the patients undergoing OPCABG.

Objective To investigate the relationship between maintaining concentration and loss of consciousness (LOC) concentration of propofol target controlled infusion (TCI) in patients undergoing heart valve replacement.Methods Thirty patients undergoing elective heart valve replacement were enrolled to receive propofol by ladder plasma TCI for anesthesia induction,8 males and 22 females.The initial plasma concentration (Cp) of propofol was set to 1.0 μg/ml,0.3 μg/ml Cp was increased every 1 min until LOC when the prediction effect-cite concentration (Ce) reached 0.5 μg/ml,then sufentanil 0.8-1.0 μg/kg and rocuronium 0.6-0.9 mg/kg were given for intubation.When BIS reached 50,Cp was decreased to the level of Ce.All the surgeries were performed under hypothermia CPB.MAP,HR,CVP,CO,SV,SVR,BIS,propofol Cp and Ce values were recorded at baseline (T0),LOC (T1),BIS reached 50 (T2),and other time points during operation (T3-T9).The correlation analysis between propofol Ce at LOC and perioperative variables were completed.Results In correlation analysis,there was a significant positive correlation between propofol Ce at LOC and baseline CO,SV (P<0.01),there was a significant negative correlation between propofol Ce at LOC and age (P<0.05),there was a significant positive correlation between propofol Ce at LOC and propofol Ce at T2-T9(P<0.01).Conclusion In patients undergoing valvular replacement,the Ce of propofol at maintenance are related to the concentration of propofol at LOC,which is helpful for adjusting the Ce of propofol at maintenance according to the Ce of propofol at LOC.

Objective To observe the effect of low tidal volume lung protective ventilation management strategy on postoperative outcome of elderly patients with poor pulmonary function after abdominal surgery.Methods Eighty patients of poor pulmonary function undergoing open gastrointestinal surgery,male 64 cases,female 16 cases,aged over 65 years old,ASA physical status Ⅱ or Ⅲ,NYHA cardiac function Ⅱ or Ⅲ grade,expected operation time 2-4 h were screened.The patients were randomly divided into 2 groups: protective ventilation management group (group P) and conventional mechanical ventilation group (group C),40 cases in each group.Multi-mode anesthetic management was performed in both groups.The respiratory parameters were adjusted according to the group after tracheal intubation,and the respiratory rate was adjusted to maintain PETCO2 35-45 mm Hg.The blood gas evaluated postoperative oxygen and postoperative spontaneous breathing recovery time,recovery time,extubation time,PACU time,gastrointestinal function recovery time,ambulation time,hospital stay and cost of hospitalization were recorded.The occurrence of major complications were observed at 30 days after surgery.Results PaO2 of group C was significantly decreased at 1 and 3 days after surgery than that before operation (P<0.05),PaCO2 of group C was significantly higher at 1 and 3 days after surgery than that of group P (P<0.05);PACU residence time of group P was (76.63±29.72) min,significantly shorter than that of group C [(93.80±42.90) min] (P<0.05);The difference spontaneous breathing recovery time,awake time,extubation time,exhaust time,ambulation time,postoperative hospitalization time and hospitalization expenses of two group was not statistically significant.Within 30 d after operation,2 cases (5%) of respiratory failure patients,3 cases (7.5%) of pneumonia in group P;5 cases (12.5%)of respiratory failure patients,3 cases (7.5%) of pneumonia,postoperative hemorrhage in 1 cases (2.5%) and 1 cases (2.5%) delirium in group C,there was no significant difference of the main complications in 30 d after operation between two groups.Conclusion Under the condition of this research,low tidal volume lung protective ventilation management strategy can improve elderly patients with poor pulmonary function after abdominal surgery postoperative oxygen and help to reduce the occurrence of postoperative adverse reactions.

Objective To evaluate the changes in the status of macrophages during the non-ventilated lung injury in the patients undergoing long-time one-lung ventilation (OLV).Methods Thirty patients of both sexes,aged 35-64 yr,weighing 50-80 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective pulmonary lobectomy for lung cancer,were divided into 2 groups (n=15 each) according to the time of OLV:short-time OLV group (＜30 min,group S) and long-time OLV group (＞2 h,group L).Anesthesia was routinely induced and maintained.Normal lung tissues around the cancer tissues from the lobe of the lung excised were obtained for microscopic examination of pathologic changes which were scored.The activated macrophages (CD68 positive),polarized M1 macrophages (CD86 positive) and polarized M2 macrophages (CD206 positive) in lung tissues were detected using immunofluorescence.The ratio of CD86 positive cells to CD206 positive cells was calculated.Results Compared with group S,lung injury scores on the non-ventilated side were significantly increased,the number of CD68,CD86 and CD206 positive cells in lung tissues was increased,and the ratio of CD86 positive cells to CD206 positive cells was increased in group L (P＜0.05).Conclusion Long-time OLV (＞2 h) can result in increased number of activated macrophages,especially the polarized M1 macrophages,which may be one of the mechanisms underlying lung injury on the non-ventilated side.

Objective To evaluate the effect of therapeutic hypercapnia on the balance between cer-ebral O2supply and demand in the patients undergoing arthroscopic shoulder surgery in the beach chair posi-tion(BCP). Methods Forty-eight patients of both sexes, aged 21-64 yr, weighing 45-80 kg, of Ameri-can Society of Anesthesiologists physical statusⅠorⅡ, scheduled for elective arthroscopic shoulder surgery in the beach chair position, were divided into 2 groups(n=24 each)using a random number table: control group(group C, end-tidal pressure of carbon dioxide 35-40 mmHg)and therapeutic hypercapnia group (group H, end-tidal pressure of carbon dioxide 45-50 mmHg). The regional cerebral oxygen saturation (rSO2)was recorded after induction and before BCP, immediately after BCP, at 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30 min after BCP and at the end of surgery(T0-12). The occurrence of cerebral desaturation events, extubation time, duration of stay in postanesthesia care unit, development of nausea and vomiting and requirement for vasoactive drugs were recorded during surgery. Results Compared with the baseline at T0, the rSO2was significantly decreased at T1-12in group C and at T2-6in group H(P<005). The rSO2was significantly higher at T1-12, and the incidence of cerebral desaturation events was lower in group H than in group C(P<005). There was no significant difference between the two groups in the extubation time, dura-tion of stay in postanesthesia care unit, incidence of nausea and vomiting or requirement for vasoactive drugs (P>005). Conclusion Therapeutic hypercapnia can improve the balance between cerebral O2supply and demand in the patients undergoing arthroscopic shoulder surgery in the BCP.

Objective To evaluate the effects of different sedation depths of propofol on postopera-tive delirium in patients undergoing cardiac valve replacement under cardiopulmonary bypass(CPB)and the relationship with regional cerebral oxygen saturation(rSO2). Methods Forty American Society of An-esthesiologists physical statusⅢorⅣpatients of both sexes, aged 26-64 yr, with body mass index of 17-25 kg∕m2, scheduled for elective aortic valve replacement with CPB, were divided into A and B groups (n=20 each)using a random number table. The infusion rate of propofol was adjusted to maintain the cor-responding anesthetic depth with 50≤BIS value<60 during CPB in group A and with 35≤BIS value<45 during CPB in group B. Bilateral rSO2was measured using the near infrared spectroscopy from admission to the operating room until the end of skin suturing. The minimum rSO2was recorded, and occurrence of low cerebral oxygen saturation(rSO2was less than 55% or the decrease in rSO2>20% of the baseline)was ob-served. Postoperative delirium was evaluated using Confusion Assessment Method for the Intensive Care Unit (ICU)from 12 h after admission to ICU until discharge from ICU. Results The incidence of postoperative delirium, low cerebral oxygen saturation and minimum rSO2were significantly lower in group B than in group A(P<005). Conclusion Maintaining 35≤ BIS value< 45 during CPB can reduce the develop-ment of postoperative delirium and is related to improving intraoperative rSO2in patients undergoing cardiac valve replacement.