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OBJECTIVE To explore the potential targets and mechanisms of the modified Baihe dihuang decoction (MBD/ BDD) applied in post-stroke depression (PSD). METHODS Network pharmacology was used to mine the potential targets and key pathways of MBD/BDD in the treatment of PSD. PSD model rats were induced by focal cerebral ischemia surgery combined with chronic unforeseen mild stress, and then were randomly divided into PSD model group, MBD/BDD group (12.6 g/kg, by raw drug), and fluoxetine hydrochloride (FLX) group (positive control, 2.3 mg/kg); a blank control group was also set up, with 8 rats in each group. Each administration group was given a corresponding medication solution by gavage once a day for 21 consecutive days. The intervention effect of MBD/BDD on depression-like symptoms in model rats was evaluated by open field and forced swimming tests. The brain tissues of rats in each group were dissected and total RNA was extracted for transcriptome sequencing and bioinformatics analysis. The mRNA and protein expressions of genes with significant changes and common neurotrophic factors were verified based on the above results. RESULTS A total of 131 MBD/BDD antidepressant-related target genes were obtained (such as IL1B and AKT1, etc.), which were closely related to neural active ligand-receptor interactions and cyclic adenosine monophosphate signaling pathway. MBD/BDD could significantly prolong or increase the total time spent and distance traveled in the central grid of qiangzhe@cqtcm.edu.cn PSD model rats, and significantly shorten the cumulative immobility time (P<0.05). After treatment with MBD/BDD, the number of genes that changed in rat brain tissue was much higher than that in the FLX group, and there were significant differences in gene profiles among the PSD model group, MBD/BDD group, and FLX group. There were 1 351 differentially expressed genes (DEGs) between the MBD/BDD group and the PSD model group, of which 178 were significantly down-regulated and 1 173 were significantly up-regulated (P<0.05). Above 1 351 DEGs were involved in neuronal differentiation, chemical synaptic transmission regulation. They were significantly enriched in axonal guidance, cholinergic synapses and neuroactive ligand-receptor interactions. The top 30 genes in terms of up-regulation in the brain tissue of rats of MBD/BDD group were all associated with neuronal proliferation, development, differentiation, and migration. After MBD/BDD intervention, the expressions of Fezf2, Arx, Ostn, Nrgn genes, brain-derived neurotrophic factor and tyrosine kinase receptor B protein in brain tissue of rats were significantly increased (P<0.05). CONCLUSIONS The anti-PSD effect of MBD/BDD may be related to the up-regulation of the expression of genes related to neuronal proliferation, development, differentiation and migration, as well as the promotion of neural structural and functional repair.
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Objective To evaluate the pharmacodynamics of cisatracurium intravenously infused during liver transplantation.Methods Twenty American Society of Anesthesiologists physical status Ⅲ or Ⅳ patients of both sexes,aged 18-60 yr,with body mass index of 20-30 kg/m2,scheduled for elective living donor liver transplantation,were enrolled in this study.Total intravenous anesthesia was used.The induction dose of cisatracurium for anesthesia was 0.15 mg/kg.When T1/T0 was restored to 10%,cisatracurium was injected intravenously at an initial rate of 1.5 μg · kg-1 · min-1.The infusion rate was adjusted according to the monitoring results of muscle relaxation,and T1/T0 was maintained at 10%.The total amount of cisatracurium infused and infusing time were recorded during dissection phase,anhepatic phase and neohepatic phase,and the consumption of cisatracurium per unit time was calculated.Before skin incision,at 5 and 30 min of anhepatic phase,at 5 and 30 min of neohepatic phase and at the end of operation,the body temperature and stroke volume variation were recorded,blood samples were collected from the radial artery for blood gas analysis and for measurement of blood K+,Mg2+ and Ca2+ concentrations,and blood samples were collected from the internal jugular vein for determination of serum creatinine (Cr),urea nitrogen (BUN) and β2 microspheres protein (β2-MG) concentrations.Results There was no significant difference in the amount of cisatracurium per unit time between dissection phase and anhepatic phase (P>0.05).The amount of cisatracurium per unit time was significantly higher in neohepatic phase than in dissection phase and anhepatic phase (P<0.05).Compared with baseline before skin incision,blood pH value was significantly decreased at 30 min of anhepatie phase and 5 min of neohepatic phase,serum Mg2+concentrations were decreased at 5 and 30 min of neohepatic phase and at the end of operation,the serum Cr,BUN and β2-MG concentrations were increased,the serum Ca2+ concentration was decreased at 5 min of anhepatic phase,and SVV was increased at 5 and 30 min of anhepatic phase (P< 0.05 or 0.01).Conclusion Muscle relaxation induced by cisatracurium infused intravenously in the anhepatic phase of liver transplantation is weakened.
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Objective@#To investigate the relationship between psoas muscle index (PMI) and early postoperative survival rate and the incidence of complications after liver transplantation in adults.@*Methods@#The clinical data of 225 patients (male, n=184; female, n=41) underwent liver transplantation at the Organ Transplantation Department of First Central Clinic Institute of Tianjin Medical University from January 2014 to December 2016 were analyzed, retrospectively.Original disease: hepatitis B liver cirrhosis(44 cases), hepatitis C cirrhosis(10 cases), autoimmune liver cirrhosis(29 cases), other benign liver diseases(24 cases), liver cirrhosis with liver cancer(116 cases), hilar cholangiocarcinoma(1 case) and hepatic vascular sarcoma(1 case). The area of bilateral psoas muscle on the lower edge level of the third lumbar vertebral body was measured through preoperative CT image.The PMI was calculated using this formula: bilateral psoas muscle area (mm2)/the square of the body height (m2). According to the receiver operating characteristic curve and cut-off values, the male and female patients were divided into low PMI group and high PMI group respectively.The χ2 test, Fisher exact test and t-test was used to compare the differences in perioperative data, survival rate and postoperative complications between the two groups, respectively.@*Results@#There were 44 patients in the low PMI group, and 181 patients in the high PMI group. ICU time was longer (82.5(62.0-128.0) hours vs.69.1(56.0-104.0) hours; P=0.006) and preoperative blood urea nitrogen level (5.86(4.35-15.52) mmol/L vs. 4.94(4.05-7.06) mmol/L; P=0.012) was higher in the low PMI group than those in the high PMI group. Incidence rates of grade 5 complication (18.2%) and grade 4a complication (18.2%) were higher in the low PMI group, and 120-day cumulative survival rate was lower than that in high PMI group(81.8% vs. 95.6%, P=0.001). On the other hand, there were no significant differences in preoperative white blood cell count level, serum creatinine level, operative time, anhepatic period time, intraoperative blood loss, and incidence of postoperative grade 3 complications between the two groups(all P>0.05).@*Conclusions@#There is a significant correlation between PMI and early postoperative survival rate and incidence of complications.Patients with lower PMI has poor prognosis after liver transplantation.
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Objective To evaluate the effects of different methods of administration on clinical pharmacodynamics of cisatracurium during liver transplantation.Methods Twenty-four ASA physical status Ⅲ patients of both sexes,aged 18-63 yr,weighing 60-88 kg,with body mass index of 20-30 kg/m2,scheduled for elective liver transplantation,were randomly divided into 2 groups (n =12 each):continuous infusion group (group C) and intermittent bolus injection group (group Ⅰ).The total intravenous anesthesia was used during surgery.When T1 recovered to 10% of control height after induction of anesthesia,continuous infusion of cisatracurium was started with an initial rate of 1.5 μg· kg-1 · min-1,and the infusion rate was manually adjusted to maintain T1 at about 10% in group C,and intermittent iv boluses of cisatracurium 0.03 mg/kg were given to maintain T1 ≤ 10% in group Ⅰ.The use of muscle relaxants was stopped immediately after peritoneum closure.The consumption of cisatracurium per minute,time for T1 to recover from 10% to 25%,recovery index and time for recovery of spontaneous breathing after surgery were recorded.Results Compared with group Ⅰ,the consumption of cisatracurium per minute was significantly reduced and the time for recovery of spontaneous breathing after surgery was shortened (P < 0.05),and no significant changes were found in the time for T1 to recover from 10% to 25% and recovery index in group C (P > 0.05).Conclusion Compared with intermittent bolus injection,continuous infusion of cisatracurium during liver transplantation is helpful in improving the clinical potency of the muscle relaxant and in reducing the occurrence of complications during anesthesia recovery period.