OBJECTIVE To investigate the anti-fatigue effect of chicory polysaccharide(CP)on mice exposed to simulated hypobaric hypoxia.METHODS Male C57BL/6J mice were randomly divided into the control group,model group,model+CP 150,300 and 600 mg·kg-1 groups.The control and model groups were given normal saline,while the CP groups were given drugs of different doses.After a 14 d pre-administration period,all the mice except the control group were exposed to a simulated alti-tude of 7 000 m in a hypobaric and hypoxic animal experimental chamber.After 7 d,a treadmill fatigue test was conducted to assess exercise endurance.The body weight and organ indexes were evaluated.The pathological changes in organs and tissues were observed via HE staining.The levels of fatigue-related and oxidative stress-related indicators were measured.The expression levels of phosphorylated AMP-activated protein kinase(p-AMPK),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),and cytochrome c oxidase Ⅳ(COXⅣ)were determined using Western blotting anal-ysis.RESULTS Compared with model group,exercise endurance was significantly enhanced,body weight and organ indexes improved,and pathological damage to the lung,liver and skeletal muscle mitigated in the model+CP 600 mg·kg-1 group.Compared with model group,the model+CP 600 mg·kg-1 group had the contents of serum lactate and blood urea nitrogen reduced,but the contents of glycogen and the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in the liver and skeletal muscle were increased.The malondialdehyde content was lowered,but the expressions of p-AMPK,PGC-1α,and COXⅣ in skeletal muscle were significantly increased.CONCLUSION CP can alleviate altitude-induced fatigue by reducing the metabolite accumulation,increasing glycogen storage,and lowering oxidative stress levels.The underlying mechanism may involve the activation of the AMPK/PGC-1αsignaling pathway.

OBJECTIVE To investigate the effect and mechanism of soluble guanylate cyclase stimulator sGC003F on cardiac function in mice with chronic heart failure(CHF).METHODS C57BL/6J male mice were randomly divided into the sham operation(sham)group,transverse aortic constriction induced CHF mouse model group,model+veliciguat(Ver,3 mg·kg-1)group(positive control)and model+sGC003F(3 and 10 mg·kg-1)group.Four weeks after modeling,drugs were ig given,once a day,for 28 d.Echocardiography was used to measure the changes in cardiac function,and the myocardial hypertrophy related indexes were calculated.The levels of serum N-terminal pro-brain natriuretic peptide(NT-pro-BNP),N-terminal pro-atrial natriuretic peptide(NT-pro-ANP),soluble guanylate cyclase(sGC),cyclic guanosine monophosphate(cGMP)and inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1β were detected by ELISA.The pathological changes of left heart tissue were observed with HE and Masson staining.Image was used to analyze the percentage of fibrosis in cardiac tissus stained with Masson.The activity of superoxide dismutase(SOD),content of malondialdehyde(MDA)in myocardial tissue,and level of nitric oxide(NO)in serum were detected by biochemical detection kits.The protein expression levels of p-mammalian target of rapamycin(p-mTOR),p-protein kinase B(p-Akt),TNF-α and IL-6 in cardiac tissue were detected by Western blotting.RESULTS Com-pared with the sham group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFs)in the model group decreased significantly(P<0.01),the cardiac structure changed significantly,the percentage of myocardial fibrosis increased significantly(P<0.05),so were serum NT-pro-BNP and NT-pro-ANP levels(P<0.01).Compared with the model group,the above indexes of the model+Ver group and the model+sGC003F 3 mg·kg-1 group were significantly improved(P<0.05,P<0.01).The sGC003F 10 mg·kg-1 group had a significant improvement in LVEF,LVFs,and NT-pro-BNP(P<0.01).Compared with the sham group,the serum levels of NO,sGC and cGMP in the model group decreased significantly(P<0.05,P<0.01).Compared with the model group,the serum levels of NO,sGC and cGMP were significantly increased in the model+sGC003F 3 mg·kg-1 group(P<0.01),but only serum cGMP levels were significantly increased in model+Ver and model+sGC003F 10 mg·kg-1 groups(P<0.01).Compared with the sham group,the serum levels of TNF-α,IL-1β and IL-6 in the model group were significantly increased(P<0.05,P<0.01).Compared with the model group,the serum levels of TNF-α,IL-1β and IL-6 were significantly decreased in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),and only the TNF-α level was significantly decreased in the model+sGC003F 10 mg·kg-1 group(P<0.01).Compared with the sham group,the SOD activity of the model group was significantly decreased(P<0.01),but the MDA content significantly increased(P<0.01).Compared with the model group,SOD and MDA were significantly improved in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),but in the model+Ver group only the SOD activity significantly increased(P<0.05).Western blotting showed that the expressions of p-mTOR,p-Akt,TNF-α and IL-6 protein in myocardial tissue of the model group were significantly higher than in the sham group(P<0.05).Compared with the model group,the expressions of the above proteins in the model+sGC003F 3 mg·kg-1 group were significantly decreased(P<0.05,P<0.01),so were the expressions of TNF-α protein in the model+sGC003F 10 mg·kg-1 group and model+Ver group(P<0.01).CONCLUSION sGC003F can improve cardiac function,and reduce myocardial fibrosis in CHF model mice,which may be related to the inhibition of myocardial oxidative stress and inflammation,and the regulation of NO/sGC/cGMP and AKT/mTOR signaling pathways.

OBJECTIVE To investigate the anti-fatigue effect of chicory polysaccharide(CP)on mice exposed to simulated hypobaric hypoxia.METHODS Male C57BL/6J mice were randomly divided into the control group,model group,model+CP 150,300 and 600 mg·kg-1 groups.The control and model groups were given normal saline,while the CP groups were given drugs of different doses.After a 14 d pre-administration period,all the mice except the control group were exposed to a simulated alti-tude of 7 000 m in a hypobaric and hypoxic animal experimental chamber.After 7 d,a treadmill fatigue test was conducted to assess exercise endurance.The body weight and organ indexes were evaluated.The pathological changes in organs and tissues were observed via HE staining.The levels of fatigue-related and oxidative stress-related indicators were measured.The expression levels of phosphorylated AMP-activated protein kinase(p-AMPK),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),and cytochrome c oxidase Ⅳ(COXⅣ)were determined using Western blotting anal-ysis.RESULTS Compared with model group,exercise endurance was significantly enhanced,body weight and organ indexes improved,and pathological damage to the lung,liver and skeletal muscle mitigated in the model+CP 600 mg·kg-1 group.Compared with model group,the model+CP 600 mg·kg-1 group had the contents of serum lactate and blood urea nitrogen reduced,but the contents of glycogen and the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in the liver and skeletal muscle were increased.The malondialdehyde content was lowered,but the expressions of p-AMPK,PGC-1α,and COXⅣ in skeletal muscle were significantly increased.CONCLUSION CP can alleviate altitude-induced fatigue by reducing the metabolite accumulation,increasing glycogen storage,and lowering oxidative stress levels.The underlying mechanism may involve the activation of the AMPK/PGC-1αsignaling pathway.

OBJECTIVE To investigate the effect and mechanism of soluble guanylate cyclase stimulator sGC003F on cardiac function in mice with chronic heart failure(CHF).METHODS C57BL/6J male mice were randomly divided into the sham operation(sham)group,transverse aortic constriction induced CHF mouse model group,model+veliciguat(Ver,3 mg·kg-1)group(positive control)and model+sGC003F(3 and 10 mg·kg-1)group.Four weeks after modeling,drugs were ig given,once a day,for 28 d.Echocardiography was used to measure the changes in cardiac function,and the myocardial hypertrophy related indexes were calculated.The levels of serum N-terminal pro-brain natriuretic peptide(NT-pro-BNP),N-terminal pro-atrial natriuretic peptide(NT-pro-ANP),soluble guanylate cyclase(sGC),cyclic guanosine monophosphate(cGMP)and inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1β were detected by ELISA.The pathological changes of left heart tissue were observed with HE and Masson staining.Image was used to analyze the percentage of fibrosis in cardiac tissus stained with Masson.The activity of superoxide dismutase(SOD),content of malondialdehyde(MDA)in myocardial tissue,and level of nitric oxide(NO)in serum were detected by biochemical detection kits.The protein expression levels of p-mammalian target of rapamycin(p-mTOR),p-protein kinase B(p-Akt),TNF-α and IL-6 in cardiac tissue were detected by Western blotting.RESULTS Com-pared with the sham group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFs)in the model group decreased significantly(P<0.01),the cardiac structure changed significantly,the percentage of myocardial fibrosis increased significantly(P<0.05),so were serum NT-pro-BNP and NT-pro-ANP levels(P<0.01).Compared with the model group,the above indexes of the model+Ver group and the model+sGC003F 3 mg·kg-1 group were significantly improved(P<0.05,P<0.01).The sGC003F 10 mg·kg-1 group had a significant improvement in LVEF,LVFs,and NT-pro-BNP(P<0.01).Compared with the sham group,the serum levels of NO,sGC and cGMP in the model group decreased significantly(P<0.05,P<0.01).Compared with the model group,the serum levels of NO,sGC and cGMP were significantly increased in the model+sGC003F 3 mg·kg-1 group(P<0.01),but only serum cGMP levels were significantly increased in model+Ver and model+sGC003F 10 mg·kg-1 groups(P<0.01).Compared with the sham group,the serum levels of TNF-α,IL-1β and IL-6 in the model group were significantly increased(P<0.05,P<0.01).Compared with the model group,the serum levels of TNF-α,IL-1β and IL-6 were significantly decreased in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),and only the TNF-α level was significantly decreased in the model+sGC003F 10 mg·kg-1 group(P<0.01).Compared with the sham group,the SOD activity of the model group was significantly decreased(P<0.01),but the MDA content significantly increased(P<0.01).Compared with the model group,SOD and MDA were significantly improved in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),but in the model+Ver group only the SOD activity significantly increased(P<0.05).Western blotting showed that the expressions of p-mTOR,p-Akt,TNF-α and IL-6 protein in myocardial tissue of the model group were significantly higher than in the sham group(P<0.05).Compared with the model group,the expressions of the above proteins in the model+sGC003F 3 mg·kg-1 group were significantly decreased(P<0.05,P<0.01),so were the expressions of TNF-α protein in the model+sGC003F 10 mg·kg-1 group and model+Ver group(P<0.01).CONCLUSION sGC003F can improve cardiac function,and reduce myocardial fibrosis in CHF model mice,which may be related to the inhibition of myocardial oxidative stress and inflammation,and the regulation of NO/sGC/cGMP and AKT/mTOR signaling pathways.

Objective To investigate the effect of intravenous injection of 20% lipid emulsion on neurotransmitters imbalance in central nerve system induced by local anesthetics.Methods Thirty adult Sprague-Dawley rats were randomly divided into two groups:normal group (group C,n =10) and local anesthetics group (group L,n =20).Based on different treatment,the rats in group L were assigned into two subgroup:control group (group S,n =10)and 20% long-chain lipid emulsion in-jection group (group I,n =10).The rats of group L were injected with 0.75% levobupivacaine at 50μl/min from the right ventricle of brain.When convulsions wave of electroencephalogram EEG ap-peared,20% long-chain lipid emulsion was administrated continuously 0.25 ml·kg-1 ·min-1 (group I)or normal saline (group S).The rats in group C were without any treatment.All the rats were con-tinously monitored by EEG,ECG and SpO 2 .The primary outcome included seizure duration and threshold and rats’mortality of postoperative 24 h.Secondary outcome included the concentrations of neurotransmitters GABA and Glu in cerebrospinal fluid,expression of NMDAR1 in cortex,Glu/GA-BA concentration ratio (Glu/GABA),and analysis the correlation between expression of Glu and NMDAR1.Results The convulsion time and mortality of rats in group S were significantly increased compared with those in group I (P <0.05).The seizure threshold of levobupivacaine was much lower in group S than group I (P <0.05).Compared with group C,the concentrations of Glu and GABA in cerebrospinal fluid,expression of NMDAR1 in hippocampus and Glu/GABA significantly increased in groups S and I(P < 0.05 ),and at same time these data in group S were significantly higher than group I (P < 0.05 ).There is a positive correlation between concentration of Glu in CSF and expression of NMDAR1 in hippocampus (r =0.884,P <0.01 ).Conclusion Intravenous infusion of 20% long-chain lipid emulsion can effectively improve neurotransmitters imbalance in central nerve system induced by intraventricular injection of local anesthetics.

Objective To investigate the effect of preemptive analgesia on postoperative cognitive function in elderly patients with abdominal surgery .Methods Totals of 127 cases of elderly patients with open major surgery were randomly divided into two groups:the experimental group (63 cases) and the control group (64 cases).The patients underwent preemptive analgesia in the experimental group , while the control group underwent conventional analgesia .VAS and MMSE were used to compare their pain and cognitive function between two groups , and dosages of fentanyl and adverse reactions were also observed .Results There were finally 60 cases in each group who had finished the study .The pain score was ( 1.86 ±0.62 ) in the experimental group and (4.03 ±0.48) in the control group six hours after operation , with statistically significant difference (t=3.67,P<0.0).The score of cognitive function was (25.42 ±0.63) in the experimental group and (21.77 ±0.50) in the control group 24 hours after operation, and the difference was statistically significant (t=3.54,P<0.05).The dosages of fentanyl was (597.94 ±82.41) μg in the experimental group and (826.47 ±113.28) μgin the control group, with statistically significant difference (t=5.42,P<0.01).The incidence of POCD was 20.00%in the experimental group and 38.33%in the control group, and the difference was statistically significant (χ2 =3.03,P<0.05).Conclusions Preemptive analgesia of electroacupunctureon elderly patients with abdominal surgery can significantly reduce their postoperative pain and improve cognitive dysfunction .

Objective To investigate the effects of controlled low central venous pressure (CLCVP) on cerebral oxygen metabolism during orthotopic liver transplantation (OLT),and study the safety of CLCVP in OLT.Method Forty-six patients subject to OLT were randomly divided into CLCVP group (CL group) and CVP group (C group).Blood samples were taken from radial artery and jugular simultaneously for blood gas analysis before operation (T1,baseline),immediately blocking inferior vena and portal vein (T2),30 min after anhepatic phase (T3),30 min after graft reperfusion (T4),2 h after graft reperfusion (T5),and 24 h after graft reperfusion (T6).Cerebral arterial oxygen content (CaO2),jugular oxygen content (CjvO2),cerebral arterial-venous oxygen content difference (Ca-jvO2),cerebral oxygen extraction rate (CERO2),and cerebral blood flow/ cerebral metabolic rate of oxygen (CBF/CMRO2) were calculated by the Fick formulae.Meanwhile,blood samples were taken from jugular simultaneously for serum creatinine (Cr) and urea nitrogen (BUN) a different time points.We also recorded the whole operation time,anhepatic phase time,volume of blood loss and transfusion,and urine volume.Results As compared with C group,CaO2,CjvO2,Ca-jvO2,SjvO2,CERO2 and CBF/CMRO2 in CL group were nearly not changed at different time pioints (P＞0.05),but in the same group,as compared with T1 and T2,the CaO2,CjvO2,Ca-jvO2 and CERO2 in T3,T4 and T5 were decreased significantly (P＜0.05),and the SjvO2 in T3,T4 and T5 was increased remarkably.The operation time and anhepatic phase time had no significant difference in both groups.As compared with C group,the volume of blood loss and transfusion in CL group were decreased (P＜0.05),and the urine volume in CL group CL was increased significantly (P＜0.05).Cr and BUN showed no significant difference in both groups and at the same time points of C group and CL group.Conclusion CLCVP can decrease volume of blood loss and transfusion,increase urine volume during OLT,and it does not change the cerebral oxygen metabolism during OLT.