ABSTRACT
Objective To explore the role and mechanism of HMGB1 in the fatty acid metabolism reprogramming and mitochondrial fusion/fission of hypoxic and nutrient-poor pancreatic cancer cells. Methods The correlation between the expression level of HMGB1 in pancreatic cancer tissue and the survival rate of pancreatic cancer patients were analyzed by GEPIA database. CCK-8 assay was used to measure cell proliferation rate, and scratch test and Transwell chamber method were carried out to detect the effects of endogenous HMGB1 on the invasion and migration abilities of human pancreatic cancer cell line Patu8988 after hypoxic and nutrient-poor treatment. Laser confocal microscope was used to observe the changes of mitochondrial morphology of Patu8988 cells. Western blot was used to detect the expression levels of mitochondrial fusion/fission and de novo fatty acid synthesis-related proteins. Results GEPIA database analysis results showed that HMGB1 was highly expressed in pancreatic cancer tissues (P < 0.01), and the expression level was negatively correlated with the survival time of pancreatic cancer patients (P=0.00097). Knockdown of HMGB1 expression could inhibit the proliferation, invasion and migration abilities of Patu8988 cells under hypoxic and nutrient-poor conditions. However, mitochondrial fission in patu8988 cells was increased. Knockdown of HMGB1 in Patu8988 cells increased the expression of fission-related protein FIS1 while decreased the expression of p-DRP1(Ser637) and fusion-related protein MFN1 and MFN2 in hypoxic and nutrient-poor environment; ACLY, p-ACLY and FASN protein expression levels were down-regulated. Conclusion Endogenous HMGB1 can promote the fusion and inhibit the fission of mitochondria in hypoxic and nutrient-poor Patu8988 cells, maintain mitochondrial morphology and function, and thereby up-regulate ACLY protein expression and phosphorylation level, promote FA synthesis, and maintain the proliferation, invasion and migration abilities of pancreatic cancer cells.
ABSTRACT
Objective To evaluate the efficacy of anesthesia with etomidate administered by TCI in combination with continuous iv remifentanil infusion titrated to maintain BIS values at 40-60 for non-cardiac surgery in a prospective randomized single-blinded multicenter controlled clinical study.Methods Two hundred and forty-four ASA Ⅰ or Ⅱ patients of both sexes aged 20-60 yr undergoing non-cardiac surgery lasting less than 3 h were randomly allocated into 2 groups:etomidate group (group E,n =123) and propofol group (group P,n =121 ).The patients were unpremedicated.A bolus of midazolam 0.03 mg/kg was injected iv immediately before induction of anesthesia.Anesthesia was induced with sufentanil 0.3-0.4 μg/kg and TCI of etomidate (effect-site concentration (Ce) =0.5-1.0 μg/ml) or propofol (Ce =3-4 μg/ml).Tracheal intubation was facilitated with rocuronium 0.9 mg/kg.The patients were mechanically ventilated (VT 8-10 ml/kg,RR 10-12 bpm,FiO2 =1 ).PETCO2 was maintained at 35-40 mm Hg.Anesthesia was maintained with TCI of etomidate ( Ce =0.3-0.8 μg/ml ) or propofol ( Ce =3-4 μg/ml) in combination with continuous iv infusion of remifentanil at 0.1-1.0 μg· kg-1 ·min-1 and intermittent iv boluses of rocuronium.BIS values were maintained at 40-60 during operation.Sufentanil 0.1 μg/kg was administered iv before skin closure.Ce at loss of consciousness,during maintenance of anesthesia and at emergence,the consumption of remifentanil and vasoactive agents,the emergence time and extubation time were recorded.The incidences of injecton pain,post-operative nausea and vomiting (PONV) and emergence agitation were measured.Results Ce of etomidate at loss of consciousness,at emergence and during maintenance of anesthesia was (0.50 ± 0.22),(0.16 ± 0.09) and 0.22-0.39 μg/ml respectively.The incidence of injection pain and the consumption of vasoactive agents were significantly lower but more remifentanil was needed in group E than in group P (P ＜0.05 or 0.01).There was no significant difference in emergence time and extubation time between the 2 groups (P ＞ 0.05).The incidence of PONV and emergence agitation were significantly higher during recovery in group E than in group P ( P ＜ 0.05 ).Conclusion The hemodynamics is stabler during operation,but the incidence of PONV and emergence agitation are significantly higher during recovery in group E than in group P.Etomidate induces little injection pain.
ABSTRACT
Objective The study was designed to compare the pharmacodynamics of rocuronium administered by continuous infusion and intermittent bolus injection Methods Fifty ASAⅠ Ⅱ patients without any neuromuscular disease undergoing elective surgery under general anesthesia were randomly divided into two groups of 25 patients each In groupⅠ patients received rocuronium by intermittent bolus injection and in group Ⅱ by continuous infusion The responses of adductor pollicis to train of four (TOF) stimulation of ulnar nerve were monitored The onset time, the time of maximal neuromuscular blockade, the spontaneous recovery from paralysis and the total dose of rocuronium were recorded Intravenous anesthesia was used for both induction and maintenance of anesthesia, no patient received reversal of block Neuromuscular blockade monitoring ended when TOF ratio(T 4/T 1)≥70% The patients were extubated when ventilation was satisfactory Results The two groups were comparable with regard to age, sex, weight and duration of operation The mean onset time after rocuronium bolus(0 6mg/kg) was (78 18?15 44) s In group Ⅱ the mean infusion rate was (6 31?1 93)?g?kg -1 ?min -1 which was not significantly different from the amount of rocuronium administered per minute (5 43?1 46)?g?kg -1 ?min -1 in groupⅠ The mean interval between two bolus injection in group Ⅰwas (29 24?6 26) min, and no significant difference was seen between intervals The spontaneous recovery from neuromuscular block was significantly faster in group Ⅱ than that in group Ⅰ Conclusions Rocuronium has no cumulative effect There was no significant difference in the amount of rocuronium administered per unit time between the two groups The spontaneous recovery from neuromuscular block is faster by continuous infusion than that by intermittent bolus injection