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Objective:To identify the risk factors for early acute lung injury (ALI) after living-related liver transplantation in pediatric patients and evaluate the value of the risk factors in prediction of ALI.Methods:Perioperative data of patients were obtained through the electronic medical records system. Patients were divided into non-ALI group and ALI group according to whether ALI occurred within the first week after surgery. The risk factors of which P values were less than 0.05 would enter the multiple logistic regression analysis to stratify ALI-related risk factors. Area under the ROC curve was used to analyze the value of the risk factors in prediction of postoperative ALI. Results:A total of 67 patients were enrolled, including 45 cases in non-ALI group and 22 cases in ALI group. Increased intraoperative blood transfusion volume and up-regulated expression of miR-122 and miR-21 were independent risk factors for the occurrence of postoperative ALI ( P<0.05), and the area under the ROC curve (95% confidence interval) of serum miR-122 and miR-21 expression was 0.946 (0.875 to 1.00), with sensitivity and specificity of 95% and 90%, respectively. Conclusions:Increased intraoperative blood transfusion volume and up-regulated expression of serum miR-122 and miR-21 are independent risk factors for early postoperative ALI, and serum miR-122 and miR-21 levels have a high value in prediction of the development of postoperative ALI in pediatric patients undergoing living-related liver transplantation.
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Objective:To compare the myocardial protection in pediatric patients undergoing living-donor liver transplantation (LDLT) performed under propofol- versus desflurane-based anesthesia. Methods:Sixty American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ pediatric patients of both sexes, aged 5-24 months, weighing 5-15 kg, scheduled for elective LDLT under general anesthesia, were divided into 2 groups ( n=30 each) using a random number table method: propofol group (group P) and desflurane anesthesia group (group D). During anesthesia maintenance, propofol 5-10 mg·kg -1·min -1 was intravenously infused in group P, desflurane 0.65 MAC-1.30 MAC was inhaled in group D. At 5 min after induction of anesthesia, at 1 h of reperfusion, at the end of surgery, at 1, 2, 3, 7 and 14 days after surgery, and on the day of discharge, the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase isoenzyme, N-terminal pro-B-type natriuretic peptide were determined by enzyme-linked immunosorbent assay, the occurrence of nausea and vomiting, agitation, and shivering, postoperative tracheal extubation time, intensive care unit stay time, and postoperative length of hospital stay were recorded within 24 h after surgery. Results:Compared with group P, the concentrations of serum high-sensitivity cardiac troponin I and creatine kinase isoenzyme were significantly decreased after surgery, the extubation time and intensive care unit stay time were shortened ( P<0.05), and no significant change was found in serum N-terminal pro-B-type natriuretic peptide concentrations, postoperative length of hospital stay and incidence of postoperative adverse effects at each time point in group D ( P>0.05). Conclusions:Desflurane has better myocardial protection than propofol in pediatric patients undergoing LDLT, which is helpful for early prognosis.
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Objective:To evaluate the effects of inhalation of high-concentration hydrogen on acute kidney injury (AKI) and mitochondrial dynamics in septic mice.Methods:One hundred and twenty-eight male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=32 each) using a random number table method: sham operation group (group Sham), sham operation + hydrogen group (group Sham+ H), sepsis AKI group, and sepsis AKI+ hydrogen group (group S-AKI+ H). A mouse model of sepsis-induced AKI was developed by cecal ligation and puncture in anesthetized animals. In Sham+ H and S-AKI+ H groups, 67% H 2+ 33% O 2 was inhaled for 1 h starting from 1 and 6 h after sham operation or developing the model, respectively. Twenty mice were selected to observe the survival at 7 days after developing the model. At 24 h after developing the model, blood samples were collected for determination of serum BUN and Cr concentrations (by colorimetric analysis), and renal tissues were obtained for determination of the contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and high mobility group protein B1 (HMGB1) (by enzyme-linked immunosorbent assay), activities of superoxide dismutase (SOD) and catalase (CAT) (by spectrophotometry) and expression of dynamin-related protein 1 (Drp1) and mitofusin 2 (Mfn2) (by Western blot). The damage to the renal tubules was scored after HE staining. Results:Compared with Sham group, the survival rate was significantly decreased, the serum BUN and Cr concentrations, renal tubular damage score and contents of TNF-α, IL-1β and HMGB1 were increased, the activities of SOD and CAT were decreased, the expression of Drp1 was up-regulated, and the expression of Mfn2 was down-regulated in S-AKI group ( P<0.05), and no significant change was found in the parameters mentioned above in Sham+ H group ( P>0.05). Compared with S-AKI group, the survival rate was significantly increased, the serum BUN and Cr concentrations, renal tubular injury score and contents of TNF-α, IL-1β and HMGB1 were decreased, the activities of SOD and CAT were increased, the expression of Drp1 was down-regulated, and the expression of Mfn2 was up-regulated in S-AKI+ H group ( P<0.05). Conclusions:Inhalation of high-concentration hydrogen can alleviate AKI in septic mice, and the mechanism may be related to inhibition of renal mitochondrial fission and promotion of mitochondrial fusion.
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Objective:To evaluate the effects of inhaling high concentration hydrogen on myocardial injury and mitochondrial biogenesis in septic mice.Methods:One hundred and twenty-eight clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=32 each) using a random number table method: sham operation group (group Sham), sham operation + hydrogen group (group Sham+ H), sepsis group (group Sep), and sepsis+ hydrogen group (group Sep+ H). The sepsis model was developed by cecal ligation and puncture in anesthetized animals. In Sham+ H and Sep+ H groups, 67% H 2 was inhaled for 1 h starting from 1 and 6 h after operation, respectively. Twenty mice in each group were randomly selected to observe the survival conditions at 7 days after operation. Blood samples were taken from the remaining mice at 24 h after operation for determination of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cardiac troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) (by enzyme-linked immunosorbent assay), for examination of the pathological changes of myocardial tissues (by HE staining), and for determination of the mitochondrial membrane potential (MMP) (by fluorescence spectrophotometry), ATP content (by luciferase assay), and expression of myocardial peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 2 (NRF2) and mitochondrial transcription factor A (TFAM) (by Western blot). Results:Compared with Sham group, the survival rate was significantly decreased, the serum concentrations of TNF-α, IL-1β, cTnI and CK-MB and pathological score were increased, the MMP and content of ATP in myocardial mitochondria were decreased, and the expression of PGC-1α, NRF2 and TFAM in myocardial tissues was down-regulated in Sep group ( P<0.05), and no significant change was found in the parameters mentioned above in Sham+ H group ( P>0.05). Compared with group Sep, the survival rate was significantly increased, the serum concentrations of TNF-α, IL-1β, cTnI and CK-MB and pathological score were decreased, the MMP and content of ATP in myocardial mitochondria were increased, and the expression of PGC-1α, NRF2 and TFAM in myocardial tissues was up-regulated in group Sep+ H ( P<0.05). Conclusions:Inhaling high concentration hydrogen can attenuate sepsis-induced myocardial injury in mice, and the mechanism may be related to promotion of mitochondrial biosynthesis and improvement in mitochondrial function.
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Objective:To evaluate the effects of berberine on necroptosis of non-alcoholic fatty liver disease in mice and its relationship with adenosine monophosphate-activated protein kinase(AMPK)/ signal transducer and activator of transcription 6(STAT6) pathway.Methods:Twenty-five 8-week-old male C57BL/6N mice were divided into control group, steatotic liver group, berberine treatment group(200 mg·kg -1·d -1), AMPK inhibitor Compound C treatment group(0.2 mg·kg -1·d -1), and STAT6 inhibitor AS1517499 treatment group(10 mg·kg -1·d -1). After 12 weeks of intervention, the mice and liver tissue were weighed, and serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) as well as liver malondialdehyde and superoxide dismutase were measured; liver tissue HE, Masson, and oil red O staining were performed. Western blotting was used to detect the expressions of necroptosis related proteins[receptor interaction protein kinase 3(RIPK3), phosphorylated(p-) mixed lineage kinase domain-like(MLKL)], AMPK, p-AMPK, and p-STAT6. Results:Compared with control group, the steatotic liver group had higher quality of liver and liver index, and higher levels of serum AST, ALT, triglyceride, TNF-α, IL-1β, and oxidative stress( P<0.05); Liver tissue was full of cavity changes and inflammatory cell infiltration, widely distributed red lipid droplets and obvious blue fiber dyeing; The expressions of RIPK3 and p-MLKL were up-regulated ( P<0.05), but the levels of p-AMPK and p-STAT6 were relatively reduced ( P<0.05). Compared with the steatotic liver group, berberine intervention decreased liver quality and liver index, improved liver function, reduced blood lipid levels, pro-inflammatory factor expression and oxidative stress level, and significantly alleviated the degree of liver steatosis and fibrosis, the levels of RIPK3 and p-MLKL ( P<0.05), while the expressions of p-AMPK and p-STAT6 were increased significantly ( P<0.05). As compared with the berberine treatment, AMPK and STAT6 inhibitor treatment could offset the protective effect of berberine on steatotic liver, moreover, the expressions of RIPK3 and p-MLKL were increased ( P<0.05). There was no statistical difference in AMPK total protein content among the five groups ( P>0.05). Conclusion:Berberine can activate AMPK/STAT6 pathway to inhibit the necroptosis of hepatocyte, thus plays a protective role on non-alcoholic fatty liver disease in mice.
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Objective:To evaluate the role of microRNA-10a (miRNA-10a) in renal ischemia-reperfusion (I/R) injury in mice and the relationship with transforming growth factor beta1 (TGF-β 1)/Smad2 signaling pathway. Methods:Twenty-four SPF healthy male adult C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=6 each) by the random number table method: sham operation group (S group), renal I/R group (IR group), renal I/R plus miRNA-10a antagonist group (I group), and renal I/R+ miRNA-10a agonist group (M group). The mouse model of renal I/R was developed by clamping the left renal pedicle for 45 min followed by reperfusion in anesthetized animals.miRNA-10a antagonist and agonist 20 nmol were injected via the tail vein once every 24 h for 3 consecutive days starting from 72 h before surgery in group M and group I, respectively, while the equal volume of normal saline was given instead in S and IR groups.Blood samples were collected from the orbital vein at 24 h of reperfusion to determine the concentrations of the serum creatinine (Scr) and blood urea nitrogen (BUN). Then the mice were sacrificed, and the kidney tissues were taken for determination of the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, contents of interleukin-1 beta (IL-β) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), and expression of TGF-β 1 and phosphorylated Smad2 (p-Smad2) (by Western blot) and for microscopic examination of the pathological changes.The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of Scr and BUN, contents of MDA, IL-1β and TNF-α in renal tissues and renal tubular damage score were significantly increased in IR, I and M groups, and the activity of SOD was significantly decreased, and the expression of TGF-β 1 and p-Smad2 was up-regulated in IR and M groups ( P<0.05). Compared with group IR, the concentrations of Scr and BUN, contents of MDA, IL-1β and TNF-α in renal tissues and renal tubular damage score were significantly decreased, the activity of SOD was increased, and the expression of TGF-β 1 and p-Smad2 was down-regulated in group I, and the concentrations of Scr and BUN, contents of MDA, IL-1β and TNF-α in renal tissues and renal tubular damage score were significantly increased, the activity of SOD was decreased, and the expression of TGF-β 1 and p-Smad2 was up-regulated in group M ( P<0.05). Compared with group I, the concentrations of Scr and BUN, contents of MDA, IL-1β and TNF-α in renal tissues and renal tubular damage score were significantly increased, the activity of SOD was decreased, and the expression of TGF-β 1 and p-Smad2 was up-regulated in group M ( P<0.05). Conclusions:miRNA-10a is involved in the process of renal I/R injury and is related to activation of TGF-β 1/Smad2 signaling pathway in mice.
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Objective:To evaluate the role of ecto-5′-nucleotidase (CD73) in endogenous protective mechanism of hepatic ischemia-reperfusion (I/R) injury in mice and the relationship with transforming growth factor beta1 (TGF-β 1)/Smad3 signaling pathway. Methods:Twenty-four SPF healthy male C57BL/6 mice, aged 8-10 weeks, weighing 20-23 g, were divided into 3 groups ( n=8 each) by the random number table method: sham operation group (S group), hepatic I/R group (IR group) and hepatic I/R plus CD73 specific inhibitor group (APCP group). The hepatic hilum was only exposed but not occluded in group S. The hepatic portal was occluded for 30 min followed by reperfusion to develop the model of hepatic I/R in anesthetized animals in group IR.CD73-specific inhibitor APCP 40 mg/kg was intraperitoneally injected, and 10 min later hepatic I/R was performed.Orbital venous blood samples were collected at 6 h of reperfusion for determination of serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations.Then the mice were sacrificed, and liver tissues were obtained for determination of the expression of CD73, TGF-β 1 and phosphorylated Smad3 (p-Smad3) (by Western blot), contents of interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), and content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) (with a visible spectrophotometer) and for microscopic examination of the pathological changes of liver tissues (with a light microscope). Results:Compared with group S, the concentrations of AST and ALT in serum and contents of IL-1β, TNF-α and MDA in liver tissues were significantly increased, the activity of SOD was decreased, and the expression of CD73, TGF-β 1 and p-Smad3 was up-regulated in IR and APCP groups ( P<0.05). Compared with group IR, the concentrations of AST and ALT in serum and contents of IL-1β, TNF-α and MDA in liver tissues were significantly increased, the activity of SOD was decreased, and the expression of CD73, TGF-β 1 and p-Smad3 in liver tissues was down-regulated in group APCP ( P<0.05). The pathological changes of liver tissues were accentuated in group APCP as compared with group IR. Conclusions:CD73 is involved in the process of endogenous protective mechanism of hepatic I/R injury in mice, which may be related to the regulation of TGF-β 1/Smad3 signaling pathway.
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Objective:To evaluate the effects of intrathecal morphine and fentanyl on interferon (IFN)-γ levels in hippocampus and plasma of rats with incisional pain.Methods:Ninety-six healthy male Sprague-Dawley rats in which intrathecal catheters were successfully inserted, weighing 180-220 g, aged 6-8 weeks, were divided into 4 groups ( n=24 each) using a random number table method: normal saline group (group NS), incisional pain group (group P), morphine and fentanyl group (group MF) and morphine and fentanyl with incisional pain group (group MFP). Incisional pain model was established in group P and group MFP.At 20 min before the model was established, a 50 μl mixture of morphine 5 μg/kg and fentanyl 0.25 μg/kg was intrathecally injected in group MF and group MFP, while normal saline 50 μl was injected intrathecally in group NS and group P. At 24 h before establishment of the model (T 0) and at 1, 6, 24, 48 and 72 h after establishment of the model (T 1-5), 6 mice were randomly selected from each group for determination of the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL). The animals were sacrificed and hippocampal tissues and blood samples from the inferior vena cava were collected for determination of IFN-γ levels in hippocampal tissues and plasma (by enzyme-linked immunosorbent assay). Results:Compared with group NS, MWT was significantly decreased and TWL was shortened at T 1-5, and IFN-γ concentration in plasma was decreased at T 2, 3 and T 5 in group P, MWT was increased and TWL was prolonged at T 1-3 in group MF, MWT was decreased and TWL was shortened at T 1-3 in group MFP, and IFN-γ concentration in plasma was decreased at T 2 in MF and MFP groups ( P<0.05). Compared with group P, MWT was increased, TWL was prolonged at T 1-5, and IFN-γ concentration in plasma was increased at T 2, 3 and T 5 in MF and MFP groups ( P<0.05). Compared with group MF, MWT was decreased and TWL was shortened at T 1-4, and IFN-γ concentration in plasma was increased at T 2 and T 3 in MFP ( P<0.05). There was no significant difference in IFN-γ concentration at each time point among the 4 groups ( P>0.05). Conclusion:Intrathecal morphine and fentanyl can increase plasma IFN-γ concentration, and improve peripheral immunosuppression.
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Objective:To evaluate the role of silencing information regulator 1 (SIRT1)/nuclear factors E2-related factor2 (Nrf2) signaling pathway in berberine-induced reduction of renal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), renal I/R group (RIR group), berberine+ I/R group (B group), berberine+ I/R+ SIRT1 inhibitor EX527 group (BE group) and berberine+ I/R+ Nrf2 inhibitor ATRA group (BA group). After the right kidney was removed, the left renal artery was clamped for 45 min followed by reperfusion to establish the model of renal I/R injury.In B, BE, and BA groups, berberine 100 mg·kg -1·d -1 was given for intragastric administration at 14 days before surgery.In group BE and group BA, EX527 5 mg·kg -1·d -1 and ATRA 10 mg·kg -1·d -1 were injected intraperitoneally at 3 days before surgery, respectively.The equal volume of normal saline was given for 14 consecutive days in group S and group RIR.Blood samples were collected from orbital vein at 24 h of reperfusion for measurement of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations, for determination of the interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) contents (by enzyme-linked immunosorbent assay) and expression of SIRT1, Nrf2, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) (by Western blot) and for examination of the pathological changes of renal tubules (with a light microscope). The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly increased in RIR, B, BE and BA groups, the expression of SIRT1, Nrf2, ASC, caspase-1 and NLRP3 was up-regulated in RIR, BE and BA groups, and the expression of SIRT1, Nrf2, caspase-1 and NLRP3 was up-regulated in group B ( P<0.05). Compared with group RIR, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly decreased in B, BE and BA groups, the expression of SIRT1 and Nrf2 in group B, Nrf2 and ASC in BE group and SIRT1, ASC and caspase-1 in BA group was up-regulated, and the expression of ASC, caspase-1 and NLRP3 in group B, SIRT1 and NLRP3 in BE group and Nrf2 in BA group was down-regulated ( P<0.05). Compared with group B, the serum concentrations of Cr and BUN, the contents of IL-1β and TNF-α and renal tubular injury score were significantly increased in BE and BA groups, the expression of ASC, caspase-1 and NLRP3 in BE and BA groups was up-regulated, and the expression of SIRT1 in BE and Nrf2 in BA groups was down-regulated ( P<0.05). Conclusion:SIRT1/Nrf2 signaling pathway is involved in the process of berberine-induced reduction of renal I/R, which is related to inhibiting pyroptosis in mice.
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The efficacy of TESSYS technique in treating the far lateral lumbar disc herniation was analyzed retrospectively.From June 2017 to June 2019, 11 patients with far lateral lumbar disc herniation underwent surgery were selected as F group, and 13 patients with central or paracentral lumbar disc herniation were selected as L group, regardless of gender, with the age of 51-66 yr.Preoperative selective nerve root block was performed under the guidance of ultrasound to determine the diseased disc, and then discectomy was performed using TESSYS technique in both groups.Pain was assessed using Visual Analogue Scale score at l day before surgery and 3 days and 1, 3 and 6 months after surgery.Patient′s function was assessed by using the Oswestry Disability Index at l day before surgery and 6 months after surgery.The therapeutic effect was evaluated using the modified Macnab criteria at 6 months after surgery.Compared with group L, no significant change was found in Visual Analogue Scale scores at each time point after surgery, Oswestry Disability Index scores at 6 months after surgery, and Macnab outcome grade at 6 months after surgery in group F ( P>0.05). In conclusion, TESSY technique can be used to treat the far lateral lumbar disc herniation.
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Objective:To evaluate the role of Toll-like receptor 4(TLR4)/Src signaling pathway in activation of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes in hippocampus in a rat model of hepatic ischemia-reperfusion (I/R).Methods:Thirty-two clean-grade healthy Sprague-Dawley rats, aged 8 weeks, weighing 200 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), hepatic I/R group (HIR group), Toll-like receptor 4 (TLR4) inhibitor TAK-242 treatment group (TAK-242 group), and Src inhibitor PP2 treatment group (PP2 group). Hepatic I/R model was established by clamping hepatic vessels for 1.5 h followed by reperfusion in anesthetized rats.TAK-242 0.5 mg/kg was injected via the tail vein at 30 min before establishing the model in group TAK-242.PP2 0.03 mg/kg was intraperitoneally injected for 3 consecutive days before establishing the model in group PP2.The animals were sacrificed at 6 h of reperfusion, and hippocampal tissues were extracted for determination of interleukin-1β (IL-1β) and interleukin-18 (IL-18) contents (by enzyme-linked immunosorbent assay), malondialdehyde (MDA) content (by TBA method), superoxide dismutase (SOD) activity (using total superoxide dismutase assay), and expression of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), c-Src, pro caspase-1, cleaved caspase-1, TLR4 and phosphorylated Src (p-Src) (Western blot). Results:Compared with Sham group, the contents of IL-1β, IL-18 and MDA were significantly increased, the SOD activity was decreased, and the expression of NLRP3, cleaved caspase-1, ASC, TLR4 and p-Src was up-regulated in the other three groups ( P<0.05). Compared with HIR group, the contents of IL-1β, IL-18 and MDA were significantly decreased, the SOD activity was increased, and the expression of NLRP3, cleaved caspase-1, ASC, TLR4 and p-Src was down-regulated in TAK-242 group and PP2 group ( P<0.05). There was no significant difference in each index between TAK-242 group and PP2 group ( P>0.05). Conclusion:The mechanism underlying activation of NLRP3 inflammasomes in hippocampus is related to activating TLR4/Src signaling pathway in a rat model of hepatic I/R.
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Objective To review the development of adult and pediatric liver transplantation in Tianjin First Center Hospital, and to enhance academic exchanges, improve technological innovation, and jointly promote the progress and maturity in the field of liver transplantation. Methods The development of liver transplantation in Tianjin First Center Hospital was analyzed. The clinical data of adult and pediatric liver transplantation from September 1998 to September 2018 were collected. The important events and technological innovation achievements of liver transplantation during the 20 years were summarized. Results The first clinical liver transplantation was attempted in Tianjin First Central Hospital in April 1980. The first long-term survival adult liver transplantation in China was completed in 1994 (11 years survival after the operation). The specialized team of liver transplantation was formally established in September 1998. The 20-year clinical exploration and progress reflected the characteristics of era changes and technological innovation during the rapid development of liver transplantation in China. Our center performed liver re-transplantation in January 1999, reduced-size pediatric liver transplantation in August 2000. In May 2001, we organized the formulation for the preventive and treatment plan for hepatitis B recurrence after liver transplantation. We performed combined liver and kidney transplantation in July 2002, split liver transplantation (SLT) in April 2004, the first domino liver transplantation (DLT) in August 2005. Pediatric living donor liver transplantation (LDLT) was initiated in October 2006, adult LDLT was carried out in August 2007. In September 2007, the first living donor combined liver and kidney transplantation from the same donor in Asia was performed. The first domino+living donor double grafts liver transplantation in the world was performed in January 2009. In March 2011, we performed laparoscopically assisted right hepatic lobe liver transplantation (LDLT) with middle hepatic vein. In May 2014, living donor laparoscopic left lateral lobe procurement was successfully established. In April 2016, simultaneous liver, pancreas and kidney multi-organ transplantation was completed. Domino donor-auxiliary liver transplantation was performed in February 2017. In December 2017, extracorporeal membrane oxygenation (ECMO)-supported liver transplantation in a patient with severe pulmonary hypertension was successfully completed. Liver transplantation combined with partial splenectomy was established in April 2018. Cross-domino liver transplantation (hypersensitive kidney transplantation with auxiliary liver transplantation+pediatric liver transplantation) was performed in May 2018. During the 20 years, the team has performed or assisted other centers in Beijing, Shanghai, Guangzhou and Shenzhen to carry out more than 10 000 cases of liver transplantations. A total of 7 043 cases of various types of liver transplantation were performed in the single center of the hospital (6 005 adult liver transplantations and 1 038 pediatric liver transplantations). Concerning adult liver transplantation, the cumulative 1-year, 3-year and 5-year survival rate from September 1998 to March 2003 were 83.1%, 73.0% and 69.0%, from April 2003 to March 2009 were 85.3%, 76.2% and 72.1% and from April 2009 to September 2018 were 87.5%, 79.2% and 75.1%, respectively. The cumulative 1-year, 3-year and 5-year survival rate for pediatric liver transplantation were 93.5%, 92.2% and 90.2%, respectively. The nucleoside (acid) analogue combined with low dose hepatitis B immunoglobulin (HBIG) was developed to prevent the recurrence of hepatitis B after liver transplantation, this plan has reduced the recurrence rate of hepatitis B and the 5-year re-infection rate of hepatitis B virus (HBV) after liver transplantation significantly. The risk assessment system for tumor recurrence after liver transplantation was established and individual treatment method was established based on this assessment system. Continuous exploration and improvement of liver transplantation for liver cancer, liver re-transplantation, liver transplantation with portal vein thrombosis, SLT, DLT and multi-organ combined transplantation have significantly improved the clinical efficacy of patients and the post-operative survival rate. Conclusions The liver transplantation team of Tianjin First Center Hospital has carried out a scientific and technological exploration on the key problems and technical difficulties of clinical liver transplantation. This work strongly has initiated and promoted the rapid development of liver transplantation in China. The restrictive barrier of hepatitis B recurrence after liver transplantation has been overcome. The risk prevention and control system of tumor recurrence after liver transplantation has been established. A series of innovative achievements that can be popularized have been achieved in the field of complex liver transplantation and expansion of donor liver source. The iterative progress and sustainable development of liver transplantation have been realized.
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Objective To evaluate the effect of propofol pretreatment on dephosphorylation of phospho-dynamin-related protein 1 (p-Drp1) Ser637 during kidney injury induced by hepatic ischemia-reperfusion (I/R) in mice.Methods Thirty healthy SPF male C57 mice,weighing 20-25 g,were divided into 3 groups (n=10 each) using a random number table method:sham operation group (group S),hepatic I/R group (group HI/R) and propofol pretreatment group (group P).Hepatic I/R was produced by occluding the blood supply to the left lateral and median lobes of liver for 60 min followed by reperfusion in anesthetized mice.In group P,1％ propofol 30 mg/kg was intraperitoneally injected at 30 min before operation,while the equal volume of normal saline was given instead in S and HI/R groups.Blood samples were collected from the left ventricle at 6 h of reperfusion for determination of the concentrations of serum blood urea nitrogen (BUN) and creatinine (Cr).Renal tissues were obtained for determination of cell apoptosis (by TUNEL) and expression of Drp1,p-Drp1 Ser637,cytochrome c (Cyt c) and cleaved caspase-3 (by Western blot) and for examination of the ultrastructure of mitochondria (by transmission electron microscopy).Apoptosis index was calculated.Results Compared with group S,the serum BUN and Cr concentrations and apoptosis index were significantly increased,the expression of p-Drp1 Ser637 was down-regulated,and the expression of Cyt c and cleaved caspase-3 was up-regulated (P＜0.05),and microscopic examination showed that mitochondria was swollen with vacuolization and mitochondrial cristae was irregularly distributed or disrupted and shortened in HI/R and P groups.Compared with group HI/R,serum BUN and Cr concentrations and apoptosis index were significantly decreased,the expression of p-Drp1 Ser637 was up-regulated,the expression of Cyt c and cleaved caspase-3 was down-regulated (P＜0.05),and the ultrastructure of mitochondria was markedly improved in group P.There was no significant difference in the expression of Drp1 in renal issues between the three groups (P＞0.05).Conclusion The mechanism by which propofol pretreatment mitigates hepatic I/R-induced kidney injury is related to inhibiting dephosphorylation of Drpl Ser637 in mice.
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Objective To explore the effect of berberine (BBR) on steatotic liver ischemia reperfusion injury and analyze the role of endoplasmic reticulum stress and autophagy .Methods Thirty-four Wistar rats were fed with a high-fat diet for 12 weeks and 2 rats were randomly selected after 8 weeks to observe pathological changes and confirm the model of steatotic liver successfully .Then before opening and closing abdominal cavity ,32 rats were divided into I/R group (normal saline was intragastrically 4 weeks before performing cold I/R treatment) ,BBR group (normal saline was replaced by BBR ,BBR was intragastrically at a dose of 300 mg·kg-1 ·d-1 weeks and others were the same as I/R group) and TG group (TG was intraperitoneally at a dose of 0 .2 mg·kg-124h pre-operation and others were the same as BBR group ) .Then the rats were sacrificed at 6h post-reperfusion .Blood samples were collected from inferior vena cava and hepatic tissues harvested .The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected ,histopathologic changes observed by Hematoxylin & Eosin (HE) staining ,oxidative stress and inflammation determined by ELISA kit and the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 detected by Western blot .Results As compared with Sham group ,the serum levels of ALT and AST were significantly higher in I/R ,BBR and TG groups (P < 0 .05) .And hepatic histological changes were severe and oxidative stress increased in parallel with the enhancement of pro-inflammation (P< 0 .05) .In BBR group ,the level of hepatic enzymes declined ,liver injury was milder ,oxidative stress decreased and pro-inflammation was lesser compared with I/R and TG groups (P< 0 .05) .Additionally ,as compared with sham group ,the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 were up-regulated in I/R and BBR groups (P < 0 .05) .TG group increased the levels of LC3 ,Beclin-1 and p62 (P< 0 .05) .Interestingly ,compared with I/R group ,BBR pretreatment down-regulated the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 (P< 0 .05) .TG group had the higher expressions of LC3 ,Beclin-1 and p62 than those of BBR group (P< 0 .05) .Conclusions BBR pretreatment can protect steatotic liver ischemia reperfusion injury .And the mechanisms may be attributed to the inhibitions of endoplasmic reticulum stress and autophagy .
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Objective To evaluate the role of necroptosis in intestinal injury induced by autologous orthotopic liver transplantation ( AOLT) in rats. Methods Twenty-four SPF adult male Sprague-Dawley rats, aged 10-12 weeks, weighing 250-280 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group ( group S) , AOLT group ( group T) and necroptosis inhibitor necrostatin-1 group ( group N) . Necrostatin-11. 0 mg∕kg and the equal volume of dimethyl sulfoxide ( DM-SO) were intraperitoneally injected at 30 min before surgery in N and T groups, respectively. Blood samples were collected from the inferior vena cava at 6 h after opening the portal vein ( at 6 h after the end of surgery in group S) for determination of serum diamine oxidase ( DAO) , D-lactic acid ( D-LA) and intestinal fatty acid binding protein ( I-FABP ) concentrations by enzyme-linked immunosorbent assay. Rats were sacrificed after blood sampling, and the intestine was removed for examination of the pathological changes ( with a light microscope ) and for determination of malondialdehyde ( MDA ) contents and superoxide dismutase ( SOD) activities ( using a spectrophotometer) , and the expression of receptor-interacting protein kinase-1 ( RIPK1) , RIPK3 and mixed lineage kinase domain-like protein ( MLKL) in intestinal tissues ( by Western blot) . Intestinal damage was assessed and scored using Chiu' s scoring system. Results Compared with group S, the serum DAO, D-LA and I-FABP concentrations, MDA content and Chiu's score were signifi-cantly increased, SOD activity was decreased, and the expression of RIPK1, RIPK3 and MLKL was up-regulated in group T ( P<0. 05) . Compared with group T, the serum DAO, D-LA and I-FABP concentra-tions, MDA content and Chiu's score were significantly decreased, the SOD activity was increased, and the expression of RIPK1, RIPK3 and MLKL was down-regulated in group N ( P<0. 05) . Conclusion Ne-croptosis is involved in the pathophysiological process of intestinal injury induced by AOLT in rats.
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Objective To evaluate the efficacy of berberine in preventing brain injury induced by hepatic ischemia-reperfusion ( I∕R) and the relationship with glycogen synthase kinase 3 beta ( GSK-3β) activity in mice. Methods Forty-eight healthy clean-grade male C57BL∕6 mice, weighing 20-25 g, were randomized into 3 groups (n=16 each) using a random number table method: sham operation group (S group), hepatic I∕R group (I∕R group) and berberine group (B group). The model of 70％ liver I∕R injury was established by clamping the portal vein and hepatic artery supplying left and middle lobes of the liver in mice anesthetized with 2％ pentobarbital sodium 40 mg∕kg. In B group, berberine 50 mg∕kg was adminis-tered through a gastric tube once a day for 7 consecutive days starting from 7 days before operation. The e-qual volume of normal saline was given instead in S group and I∕R group. The mice were sacrificed at 6 h af-ter reperfusion, brains were removed and hippocampal tissues were harvested for microscopic examination of pathological changes ( with a light microscope) and for determination of cell apoptosis ( by TUNEL) , super-oxide dismutase ( SOD ) activity ( by xanthine oxidase method ) , malondialdehyde ( MDA ) content ( by thiobarbituric acid colorimetric method) , expression of phosphorylated GSK-3β ( p-GSK-3β) and GSK-3β(by Western blot), and opening of mitochondrial permeability transition pore (mPTP). The apoptosis in-dex and p-GSK-3β∕GSK-3β ratio were calculated. Results Compared with S group, the apoptosis index and MDA content were significantly increased, SOD activity and p-GSK-3β∕GSK-3β ratio were decreased, and mPTP opening was increased in I∕R and B groups ( P<0. 05) . Compared with group I∕R, the apoptosis index and MDA content were significantly decreased, SOD activity and p-GSK-3β∕GSK-3β ratio were in-creased, mPTP opening was decreased (P<0. 05), and the pathological changes of hippocampal tissues were significantly attenuated in B group. Conclusion Berberine can prevent the brain injury induced by he-patic I∕R, and the mechanism may be related to inhibiting GSK-3βactivity and thus inhibiting mPTP open-ing in mice.
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Objective To evaluate the optimum compatibility of nalbufine combined with ropivacaine for patient-controlled epidural analgesia (PCEA) after cesarean section.Methods A total of 100 parturients who were at full term with a singleton fetus,aged 24-35 yr,with body mass index of 29-33 kg/m2,of American society of Anesthesiologists physical status Ⅱ,scheduled for elective cesarean section under combined spinal-epidural anesthesia,were divided into 4 groups (n =25 each) using a random number table method:sufentanil 0.5 μg/ml plus 0.15％ ropivacaine group (SR group),nalbufine at final concentration of 0.2 mg/ml plus 0.15％ ropivacaine group (N1 R group),nalbufine at final concentration of 0.4 mg/ml plus 0.15％ ropivacaine group (N2R group) and nalbufine at final concentration of 0.4 mg/ml plus 0.1％ ropivacaine group (N3Rgroup).PCEA solution was prepared correspondingly after surgery,and all the drugs were diluted to 100 ml in normal saline in each group.The PCA pump was set up to deliver a 0.5 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h.Visual analog scale scores of incisional pain and anduterine contraction pain were maintained＜4.Ramsay sedation scores were recorded at 8,12,24 and 48 h after surgery.The total pressing times of PCEA were recorded within 48 h after surgery.The development of adverse reactions such as nausea,vomiting,skin itching,numbness of lower extremity,urinary retention and respiratory depression was recorded in the analgesia period.Venous blood samples were collected before surgery and at 24 and 48 h after surgery for determination of plasma prolactin concentrations,and the time of colostrum was recorded.Neonatal nerve and adaptive capacity was assessed and scored.Results Compared with group SR,the total pressing times of PCEA were significantly reduced in N2R and N3R groups (P＜0.05),and no significant change was found in the total pressing times of PCEA in group N1R (P＞0.05).Compared with group N1R,the total pressing times of PCEA were significantly reduced in N2R and N3 R groups (P＜0.05).There was no significant difference in the total pressing times of PCEA between group N2R and group N3R (P＞0.05).The Ramsay sedation score was 2 in four groups.There was no significant difference in numbness of lower extremity,plasma prolactin concentrations or neonatal nerve and adaptive capacity scores among four groups (P＞0.05).Conclusion Nalbufine at final concentraction of 0.4 mg/ml mixed with 0.1％ ropivacaine is the optimum compatibility when used for PCEA after cesarean section.
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Objective To evaluate the efficacy of transversus abdominis plane (TAP) block combined with butopenol patient-controlled intravenous analgesia (PCIA) for analgesia after cesarean section under general anesthesia.Methods Ninety American Society of Anesthesiologists physical status Ⅰ or Ⅱ parturients,aged 18-42 yr,weighing 52-88 kg,at 38-42 weeks of gestation,scheduled for elective cesarean section under general anesthesia,were divided into 3 groups (n=30 each) using a random number table method:TAP block group (group TAP),butopenol PCIA group (group B) and TAP block plus butopenol PCIA group (group TB).In group TAP,bilateral TAP blocks were performed under ultrasound guidance at the end of surgery,and 0.375％ ropivacaine 20 ml was injected into each side.In group B,butopenol 1 mg was intravenously injected at 30 min before the end of operation,PCIA was performed at the end of surgery,PCIA solution contained butopenol 8 mg and ondansetron 8 mg (diluted to 100 ml in sodium chloride injection),and the PCIA pump was set up to deliver a 0.5 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h.Butopenol 1 mg was intravenously injected at 30 min before the end of operation,and TAP block in combination with butopenol PCIA was performed at the end of operation in group TB.When the postoperative visual analog scale score was greater than or equal to 4 points,morphine 10 mg was intramuscularly injected as rescue analgesic.The requirement for morphine was recorded within 48 h after operation.The occurrence of agitation during emergence from anesthesia and adverse reactions within 48 h after operation were also recorded.Results No adverse reactions such as hematoma at the puncture site or local anesthetic intoxication were observed in TAP group and TB group.Compared with group TAP,the incidence of postoperative shivering and requirement for morphine were significantly decreased in group TB (P＜0.05).The incidence of postoperative nausea and v omiting and requirement for morphine were significantly lower in group TB than in group B (P＜0.05).Conclusion The combination of TAP block and butopenol PCIA exerts better efficacy for analgesia after cesarean section under general anesthesia than either alone.
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Objective To evaluate the effect of berberine on fatty liver ischemia-repeffusion (I/R) injury and the relationship with endoplasmic reticulum stress in liver tissues.Methods Thirty-two male Wistar rats,aged 4 weeks,weighing 100-150 g,were divided into 4 groups (n=8 each) using a random number table method:control group (group C),fatty liver group (group FL),I/R group and berberine group (group BBR).Rats were fed a normal fat diet for 12 weeks,normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and rats only underwent simple laparotomy in group C.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,and the other treatments were similar to those previously described in group C.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and then the model of liver I/R injury was established in group I/R.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,berberine solution (300 mg/kg) 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and then the model of liver I/R injury was established in group BBR.Hepatic ischemia was induced by clamping the portal vein,hepatic artery,right gastric vein,and supra-and inferior-hepatic vena cava to perform cold perfusion with 4 ℃ lactated Ringer's solution lasting for 30 min,followed by reperfusion.The serum triglyceride (TG) concentrations were determined after 4,8 and 12 weeks of diet.Blood samples were collected at 6 h of reperfusion for measurement of serum aspartate transminase (AST) and alanine transaminase (ALT) concentrations.Livers were removed after blood sampling at 6 h of reperfusion and liver tissues were obtained and stained with oil red O and haematoxylin and eosin for examination of pathological changes and for determination of the expression of Bip,CCAAT/enhancer-binding protein homologous protein (CHOP),protein kinase RNA-like endoplasmic reticulum kinase (PERK) and phosphorylated PERK (p-PERK) (by Western blot).p-PERK/PERK ratio was calculated.Results Compared with group C,the serum TG,ALT and AST concentrations were significantly increased,the expression of Bip and CHOP was up-regulated,p-PERK/PERK ratio was increased (P＜0.05),lipid deposition was increased,and liver steatosis was found in group FL.Compared with group FL,the serum AST and ALT concentrations were significantly increased,the expression of Bip and CHOP was up-regulated,pPERK/PERK ratio was increased (P＜0.05),and the pathological changes of liver tissues were accentuated in group I/R.Compared with group I/R,the serum TG,ALT and AST concentrations were significantly decreased,the expression of Bip and CHOP was down-regulated,p-PERK/PERK ratio was decreased (P＜ 0.05),lipid deposition was reduced,and the pathological changes of liver tissues were significantly attenuated in group BBR.Conclusion Berberine can ameliorate fatty liver I/R injury,and the mechanism may be related to inhibiting endoplasmic reticulum stress in liver tissues of rats.
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Objective To investigate the effects of ulinastatin preconditioning combined with postconditioning on kidney injury of pediatric patients undergoing living donor liver transplantation (LDLT) and the underlying mechanism.Methods Forty pediatric patients with biliary atresia,scheduled for LDLT,were randomly divided into two groups (n =20 each):the ulinastatin group and the control group using a random number table.Ulinastatin (20 000 U/kg) was diluted into 10 000 U/mL with normal saline,and it was then injected intravenously in 2 parts (1/2 was given before skin incision;1/2 at 5 min before portal vein declamping) in the ulinastatin group.In the control group,the equal volume of normal saline was given instead of ulinastatin.Blood samples and urine specimens were taken from the central vein immediately before skin incision (T0,baseline),at 30 min of anhepatic period (T1),at 1 h of neohepatic period (T2),at the end of surgery (T3),and 24 h after surgery (T4) for the determination.The concentrations of serum and urine β2-microglobulin (β2-MG) were measured using an immunonephelometric method.The levels of serum TNF-α,IL-6 and IL-18 were measured using an ELISA method.The serum concentrations of creatinine (Cr) and blood urea nitrogen (BUN) were measured using a colorimetry method.Results The serum Cr,BUN,β2-MG and urine β2-MG concentrations were higher at T2-4 than at T0 in the two groups (P＜0.05 or 0.01).As compared with the control group,the serum Cr,BUN,β2-MG and urine β2-MG concentrations were significantly decreased in the ulinastatin group (P＜0.05 or 0.01).The serum levels of TNF-α,IL-6 and IL-18 were higher at T2 4 than at T0 in the two groups (P＜0.05 or 0.01).As compared with the control group,the serum levels of TNF-α,IL-6,and IL-18 were significantly decreased in the ulinastatin group (P＜0.05 or 0.01).Conclusion Ulinastatin preconditioning combined with postconditioning can alleviate kidney injury in pediatric patients undergoing LDLT to some extent,which may be related to inhibiting the excessive release of inflammatory factors.