Objective To investigate the effect of creatine phosphate on perioperative myocardial injury caused by living donor liver transplantation(LDLT)in adult patients.Methods Forty ASA Ⅱ -Ⅳ patients(liver function Child-Pugh grade B or C)aged 45-62 yr weighing 47-91 kg undergoing LDLT were randomly divided into 2 groups(n = 20 each): control group(group C)and creatine phosphate group(group CP).In group CP,creatine phosphate 30 mg/kg was injected intravenously at skin incision followed by creatine phosphate infusion at 4 mg· kg- 1 · h- 1 until the end of surgery.In group C,equal volume of normal saline was infused instead of creatine phosphate.HR,MAP,CVP,PCWP,CO and SvO2 were recorded immediately 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.Blood samples were taken from central vein immediately before skin incision(baseline,T0),at 30 min of anhepatic phase(T1),at 30min of neohepatic phase(T2),at the end of operation(T3)and at 4 and 24 h after operation(T4,5)for determination of serum cardiac troponin I(cTnI)and creatine kinase MB(CK-MB)concentrations and lactate dehydrogenase(LDH)activity.Postoperative adverse events were recorded.Results The serum cTnI and CK-MB concentrations and LDH activity were significantly increased at T2-5 as compared with the baseline value at T0 in both groups(P ＜0.05 or 0.01).MAP and CO were significantly higher from 5 min of neohepatic phase to the end of operation,the serum cTnI and CK-MB concentrations and LDH activity were significantly lower at T2-5,and the incidence of ventricular arrhythmia was significantly lower in group CP than in group C(P ＜ 0.05 or 0.01).Conclusion Creatine phosphate can attenuate perioperative myocardial injury caused by LDLT in adult patients.

Objective To confirm the protective effect of berberine (BBR) on cold ischemia reperfusion (I/R)-induced liver injury and to show whether the hepatic protection conferred by BBR involves the activation of phosphatidylinositol 3 kinase (PI3K) / protein kinase B (Akt)/mammalian target of rapamycin(mTOR) signal pathway.Method Adult male Sprague-Dawley rats were assigned randomly to four groups:BBR group (BBR was intragastrically administered at a dose of 100 mg·kg-1 · d-1 2 weeks before hepatic cold I/R treatment),dimethyl sulfoxide (DMSO) group (BBR was replaced by DMSO,and others were the same as BBR group),I/R group (BBR was replaced by normal saline,and others were the same as BBR group) and sham group (normal saline was administered 2 weeks before opening and closing abdomen treatment).Then the rats were sacrificed at 3,6,and 24 h after reperfusion.The liver function,oxidative stress level,apoptosis rate,and the expression of PI3K/Akt/mTOR related pathway proteins were assayed.Result As compared with sham group,the I/R-induced liver tissue displayed severe lobular distortion with widespread necrosis,high level of oxidative stress and apoptosis rate.As compared with I/R group,BBR dramatically attenuated the histopathologic damage,restored the liver function and decreased the oxidative stress level.Simultaneously,BBR significantly ameliorated the apoptosis by decreasing the apoptosis rate,increasing the Bcl-2/Bax ratio and inhibiting caspase-3 activity in rats subjected to hepatic I/R.The expression of p-Akt was effectively upregulated with the inhibited expression of p-mTOR.Conclusion Our result provides robust in vivo evidence that BBR can prevent I/R-induced oxidative stress and apoptosis.The mechanisms involved can be attributed to the activation of P]3K/Akt/mTOR signal pathway.

Kidney plays an important role in maintaining the homeostasis as an important excretory and endocrine organ.The occurrence and development of kidney disease is closely associated with glomerular filtration barrier dysfunction and renal interstitial remodeling.Matrix metalloproteinase-9 (MMP-9),a major enzyme in the extracellular matrix (ECM),plays an important role in the process of kidney disease by regulating the ECM components and its interaction with cytokines.The paper reviews the pathophysiology of MMP-9 in glomerular filtration barrier dysfunction and renal fibrosis to provide a theoretical basis for clinical treatment of kidney disease.

Objective To evaluate the effect of dexmedetomidine on myocardial injury in pediatric patients undergoing living-related liver transplantation. Methods Fifty-eight pediatric patients of both sexes,aged 5-20 months,weighing 4.5-15.0kg,of American Society of Anesthesiologists physical status Ⅲ or Ⅳ,scheduled for elective living-related liver transplantation,were divided into 2 groups(n=29 each)using a random number table:control group(group C)and dexmedetomidine group(group D).In group D,dexmedetomidine was intravenously infused at a dose of 0.5 μg/kg over 10min starting from the time point immediately before skin incision,followed by an infusion of 0.8 μg·kg-1·h-1 until the end of surgery. The equal volume of normal saline was given instead in group C. Immediately before skin incision(baseline,T0),at 10min of anhepatic phase(T1),at 30min of neohepatic phase(T2)and at the end of surgery(T3),blood samples were obtained from the central vein for determination of serum cardiac troponin I(cTnI),lactate dehydrogenase(LDH),alpha-hydroxybutyrate dehydrogenase(α-HBDH),interleukin-6(IL-6)and IL-10 concentrations. The changing rate of serum cTnI concentrations were calculated at T2. The occurrence of myocardial ischemia and ventricular premature beat and requirement for dopamine were recorded during surgery. Results Compared with the baseline at T0,the serum concentrations of cTnI,LDH and α-HBDH were significantly increased at T2,3,and the serum concentrations of IL-6 and IL-10 were increased at T1-3 in both groups(P<0.05).Compared with group C,the serum concentrations of cTnI,LDH,α-HBDH and IL-6 were significantly decreased at T2,3,the serum concentration of IL-10 was increased at T1-3,the changing rate of serum cTnI concentrations was decreased(P<0.05),and no significant change was found in the incidence of myocardial ischemia and ventricular premature beat and requirement for dopamine in group D(P>0.05).Conclusion Dexmedetomidine can attenuate the myocardial injury to some extent in pediatric patients undergoing living-related liver transplantation.

Objective To evaluate the effect of dexmedetomidine pretreatment on activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway during intestinal injury in rats undergoing liver transplantation.Methods Thirty-two pathogen-free healthy adult male Sprague-Dawley rats,weighing 220-250 g,aged 8-10 weeks,were divided into 4 groups (n =8 each) using a random number table:sham operation group (S group),liver transplantation group (LT group),dexmedetomidine pretreatment group (D group) and dexmedetomidine plus atipamezole (specific α2-adrenergic receptor antagonist) group (D+A group).The model of liver transplantation was established in LT,D and D+A groups except group S.In group D,dexmedetomidine 50 μg/kg was injected intraperitoneally at 30 min before skin incision.In group D+A,atipamzole 250 μg/kg was injected intraperitoneally at 5 min before administration of dexmedetomidine.At 6 h of reperfusion,blood samples were collected from the inferior vena cava for determination of serum concentrations of intestinal fatty acid binding protein (iFABP),lipopolysaccharide (LPS),tumor necrosis factor-alpha (TNF-ct) and high-mobility group box 1 protein (HMGB1).Intestinal specimens were then obtained for examination of the pathological changes of intestinal tissues (under light microscope) and for determination of the expression of activated caspase-3,phosphorylated JAK2 (p-JAK2),phosphorylated STAT1 (p-STAT1) and phosphorylated STAT3 (p-STAT3).Intestinal damage was assessed and scored.Wet/dry weight ratio (W/D ratio) was calculated.Results Compared with group S,the concentrations of iFABP,LPS,TNF-α and HMGB1 in serum,intestinal damage scores and W/D ratio were significantly increased,and the expression of activated caspase-3,p-JAK2,pSTATI and p-STAT3 in intestinal tissues was up-regulated in LT and D groups (P＜0.05).Compared with group LT,the concentrations of iFABP,LPS,TNF-cα and HMGB1 in serum,intestinal damage scores and W/D ratio were significantly decreased,and the expression of activated caspase-3,p-JAK2,p-STAT1 and p-STAT3 in intestinal tissues was down-regulated in group D (P＜0.05).Compared with group D,the concentrations of iFABP,LPS,TNF-cα and HMGB1 in serum,intestinal damage scores and W/D ratio were significantly increased,and the expression of activated caspase-3,p-JAK2,p-STAT1 and p-STAT3 in intestinal tissues was up-regulated in group D+A (P＜0.05).The pathological changes of intestinal tissues were significantly attenuated in group D as compared with group LT.Conclusion The mechanism by which dexmedetomidine pretreatment reduces intestinal injury may be related to inhibition of JAK/STAT signaling pathway activation in rats undergoing liver transplantation.

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.

Objective To evaluate the impact of cardiac troponin Ⅰ (cTnI) on acute lung injury in pediatric living donor liver transplant children with biliary atresia.Methods The clinical data of 112 pediatric living donor liver transplant recipients with biliary atresia in Tianjin First Central Hospital from February 2011 to September 2015 were retrospectively reviewed.Fifty-five recipients with cTnI ≥0.07 μg/L served as high-cTnI group and 57 recipients with cTnI group ＜0.07μg/L as normalcTnI group.The clinical data between two groups were compared and the association between serum cTnI level and acute lung injury after living-donor liver transplantation was evaluated by logistic regression analysis.Results The percentage of acute lung injury after pediatric living donor liver transplantation in high-cTnI group and normal-cTnI group was 31.6％ and 9.1％,respectively.Intratransplant cTnI ≥0.07μg/L (OR =4.489,confidence interval 1.170-17.226) was the risk factor for acute lung injury after transplantation.The value of cTnI showed the positive correlation with preoperative PELD scores (OR =4.489,confidence interval 1.170-17.226).Conclusions Intratransplant cTnI level was the significant prognostic risk factor in acute lung injury after pediatric living-donor liver transplantation for children with biliary atresia.The cTnI level was associated with preoperative PELD scores.

Objective To compare the severity of periopemtive myocardial injury caused by live donorliver transplantation (LDLT) performed under sevoflurane and pmpofol combined anesthesia in adult patients. Methods Forty ASA Ⅱ-Ⅳ patients(liver function Child-Pugh grade B or C)aged 40-67 yr weighing 47-95 kgundergoing right lobe LDLT were randomly divided into 2 groups(n=20 each):sevoflurane combined anesthesiagroup (group S) and propofol combined anesthesia group(group P).Anesthesia was maintained with 1.6%-3.0% sevoflurane in group S or PCI of pmpofol(Cp 2-4μg/ml)in group P combined with sufentanil infusion at 0.5- 1.0 μg·kg-1·h-1 and intermittent iv boluses of cisatracurium in both groups.MAP,HR,CVP,MPAP,PCWP, CO and mixed venous O2 saturation(S(v)O2)were recorded before skin incision at 5 and 30 min of anhepatic phaseand 5 and 30 min of ncohepatic phase and the end of operation:Blood samples were taken from central vein beforeskin incision(T0,baseline)at 30 min of anhepatic phase(T1),30 min of neohepatic phase(T2),the end ofsurgery (T3) and 24,48,72 h after operation (T4,5,6) for determination of serum concentrations of cardiactroponin I (cTnI) and creatine kinase MB(CK-MB).Postoperative adverse effects were recorded.Results Thetwo groups were comparable with respect to 8ex ratio(M/F),age,body weight,duration of operation,duration ofanhepatic phase,blood loss,dopamine and nitroglycerin consumption.There was no significant difference in MAP, HR,CVP,MPAP,PCWP,CO and S(v)O2 between the two groups.The serum concentrations of cTnI and CK-MB were significantly increased at T2-5 as compared with the baseline value at T0 in both groups. There was no significant difference in serum concentrations of cTnI and CK-MB and in the incidence of myocardial ischemia and arrythmia between the two groups. Conclusion Sevoflurane and propofol combined anesthesia have similar effects on myocardial injury caused by LDLT in adult patients.

Objective To observe the effect of hypothermia in reperfusion stage on prognosis during adult liver transplantation.Methods Data of 107 patients (62 males, 45 females, aged 25～65 years, ASA physical status Ⅲ or Ⅳ) underwent adult liver transplantation from January 2015 to December 2016 in our hospital were retrospectively analyzed.The temperature at the time of anesthesia induction (T0), skin incision (T1), anhepatic phase immediately (T2), immediate reperfusion (T3), 5 min after reperfusion (T4), abdomen-closing (T5) and the end of surgery (T6) were recorded to observe the trend of overall temperature change.Patients were devided into normal temperature group (core temperature was≥35℃ or ＜35℃ but the duration was less than 5 min in reperfusion period) and hypothemia group (core body temperature was ＜35℃ and the duration was>5 min) to compare difference between the two groups of perioperative blood loss, urine volume, postoperative extubation time, ICU staying time and hospitalization time.The influence of hypothermia during the new liver phase (T4-T6) on prognosis and correlation between duration of hypothermia and blood loss, urine volume, postoperative extubation time, ICU staying time and hospitalization time were analyzed.Results This study found that during the perioperative adult liver transplantation, the body temperature showed a decreasing trend first (T0-T4) and then an increasing one (T4-T6).The body temperature droped to the lowest at T4, which was lower than the normal body temperarure.Compared with T0, the temperature decreased obviously at T2-T5 (P＜0.05);Compared to normal temperature group, the amount of bleeding was more and the extubation time was longer in hypothermia group (P＜0.05), and there was no significant difference in urine volume, ICU staying time and hospitalization time between the two groups.There were positive correlations between the time of hypothermia and bleeding, extubation time, ICU staying time and negative correlations with urine output, while no obvious relations with postoperative hospital staying time.Conclusion During the perioperative liver transplantation, hypothermia increased the blood loss and postoperative extubation time.The longer the hypothermia time is, the poorer the prognosis is.

Objective To evaluate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in attenuation of ischemia injury by hydrogen-rich University of Wisconsin (HRUW) solution during cold storage of rat donor kidneys.Methods Forty healthy adult male Wistar rats,weighing 200-250 g,were divided into 4 groups (n =10 each) using a random number table:control group (group C),University of Wisconsin (UW) solution group (group UW),HRUW solution group (group HRUW) and Nrf2 inhibitor all-trans retinoic acid (ATRA) group (group ATRA).ATRA 7 mg/kg was intraperitioneally injected once a day for 2 consecutive days,kidneys were isolated and underwent cold storage at 8 h after the last administration,and kidneys were stored in HRUW solution for 48 h at 4 ℃C in group ATRA.In UW and HRUW groups,the equal volume of normal saline was intraperitioneally injected instead,and isolated kidneys were stored in UW solution and HRUW solution for 48 h at 4 ℃C,respectively.Kidney specimens were obtained for microscopic examination and for determination of tumor necrosis factoralpha (TNF-α),interleukin-lbeta (IL-1β3),high-mobility group box 1 protein (HMGB1),IL-10 and 8-iso-prostaglandin F2α (8-iso-PGF2α) contents (by enzyme-linked immunosorlbent assay),superoxide dismutase (SOD) and catalase (CAT) activities (using spectrophotometry),and expression of Nrf2,heme oxygenase-1 (HO-1),Bcl-2,Bax and caspase-3 in renal tissues (by using Western blot).The damage to the renal tubules was scored.Results Compared with group C,renal tubular damage scores were signifieantly increased,TNF-α,IL-1β,HMGB1 and 8-iso-PGF2α contents were increased,IL-10 contents were decreased,the expression of Nrf2 and HO-1 was up-regulated,SOD and CAT activities were decreased,the expression of Bcl-2 was down-regulated,and the expression of Bax and caspase-3 was upregulated in group UW (P＜0.05 or 0.01).Compared w,ith group UW,renal tubular damage scores were significantly decreased,TNF-α,IL-1β,HMGB1 and 8-iso-PGF2α contents were decreased,IL-10 contents were increased,the expression of Nrf2 and HO-1 was up-regulated,SOD and CAT activities were increased,the expression of Bcl-2 was up-regulated,and the expression of Bax and caspase-3 was down-regulated in group HRUW,and the expression of Nrf2 and Bcl-2 was up-regulated (P＜0.05),and no significant change was found in the other parameters in group ATRA (P＞0.05).Compared witb group HRUW,renal tubular damage seores were significantly increased,TNF-α,IL-1β,HMGB1 and 8-iso-PGF2α contents were increased,IL-10 contents were decreased,the expression of HO-1 and Bcl-2 was down-regulated,SOD and CAT activities were decreased,and the expression of Bax and caspase-3 was up-regulated in group ATRA.Conclusion HRUW solution reduces inflammatory responses,oxidative damage and cell apoptosis during cold storage of rat donor kidneys,and the mechanism by which HRUW solution attenuates ischemia injury is related to activation of Nrf2 signaling pathway.