Objective To analyze and compare the dosage,blood concentration and metabolic characteristics of Tacrolimus (Tac) for pediatric patients who underwent living related liver transplantation (LRLT) or donation after cardiac death liver transplantation (DDLT).Methods The clinical data of 75 liver transplantation pediatric patients from October 2012 to August 2015 were retrospectively analyzed.According to the different source of donors,the recipients were divided into two groups:LRLT group (40 cases) and DDLT group (35 cases).Results (1) Under the condition of same initial Tac dosage,the Tac dosage in LRLT group was less than in DDLT group during the first 28 days post-transplantation (P＞ 0.05).However,the Tac dosage in DDLT group was significantly higher than in LRLT group on the second and third months after sugery (P =0.000).(2) Correlation analysis revealed that graft-recipient body weight ratio (GRWR) was correlated with Tac dosage (mg·kg-1 ·d-1) on the 14th day postoperative (LRLT group:r=0.579,P＜0.05;DDLT group:r =0.583,P＜0.05) and Tac concentration/dosage ratio (LRLT group:r =-0.607,P＜0.05;DDLT group:r=-0.680,P＜0.05).Conclusion Tac has a satisfactory anti-rejection effect on liver transplantation pediatric patients while the metabolism varied with each individual.There is a positive correlation between the early Tac dosage and the GRWR in both groups.It is necessary to set individualized Tac administration regimen according to the metabolic characteristics and GRWR.

Objective:To study the use of digital subtraction angiography (DSA) guided transnasal ileus tube placement in management of abdominal compartment syndrome (ACS) after liver transplantation.Methods:From January 2015 to December 2019, a total of 30 patients who developed ACS after liver transplantation who were admitted to the Transplantation Intensive Care Unit of Tianjin First Central Hospital were retrospectively studied. According to the way of decompression, these patients were divided into the study group and the control group. Patients in the control group were treated with conventional abdominal decompression, while patients in the study group were treated with DSA guided transnasal ileus tube placement based on management principles developed in conventional abdominal decompression. Changes in intra-abdominal pressure, treatment efficacy rates and liver functions were monitored in the two groups up to 7 days after abdominal decompression.Results:There were 23 males and 7 females, aged (53.4±11.6) years. After treatment, the IAP, portal venous blood flow velocity, bile drainage volume, ALT and AST in the study group were significantly better when compared with the findings before treatment: [IAP: (7.13±3.87) vs (22.73±2.09) mmHg, portal vein blood flow velocity: (34.76±10.31) vs (21.45±6.47) cm/s, bile drainage volume: (198.43±19.94) vs (80.72±9.52) ml/d, ALT: (158.92±67.56) vs (278.73±99.17) U/L, AST: (79.36±15.63) vs (196.71±89.05) U/L], ( P<0.05). After treatment, when compared with the control group, the IAP, portal vein blood flow velocity, bile drainage and TBil in the study group were significantly better [IAP: (7.13±3.87) vs (13.47±6.19) mmHg, portal vein blood flow velocity: (34.76±10.31) vs (24.98±8.54) cm/s, bile drainage: (198.43±19.94) vs (108.73±21.30) ml/d, TBil: (258.85±91.95) vs (343.69±89.45) μmol/L], ( P<0.05). In the control group, the IAP significantly decreased on the fourth day after treatment, ( P<0.05); compared with the significant difference in the study group on the second day after treatment ( P<0.05). After 7 days of treatment, the efficacy rate of the control group was 46.7% (7/15), compared to 86.7% (13/15) in the study group. The difference between the two groups was significant (χ 2=5.400, P<0.05). Conclusion:DSA guided transnasal ileus tube placement for treatment of abdominal compartment syndrome after liver transplantation resulted in a better treatment efficacy rate than conventional treatment.

Objective To probe the correlation between preoperative pulmonary dysfunction and postoperative pulmonary complications in patients of orthotopic liver transplantation. Methods From August 2008 to June 2009, 71 orthotopic liver transplantation patients were studied. Preoperative pulmonary function and its relationship with postoperative pulmonary complications were analyzed.Results Preoperatively 65 out of 71 patients had abnormal lung functions, suffering from pulmonary diffusing capacity reduction (65 cases, 91.5% ), followed by reduction of restrictive ventilation function (30 cases, 42. 2% ), small airway function reduction ( 28 cases, 39.4% ), and obstructive ventilatory function reduction (21 cases, 29. 6% ). The incidence of postoperative pulmonary complications was 56. 3% including: pulmonary atelectasis, pneumonia, acute respiratory failure. The incidence of posttransplantation pulmonary complications in patients with pulmonary restrictive or obstructive ventilation function reduction was higher than in normal group (x2 = 6.703, P= 0.010; x2 = 4.768, P = 0.029), and there was significant difference in pulmonary complication rate between groups of moderate and severe diffusing capacity reduction and mild reduction and normal range (x2 = 8.478, P = 0.004 ).Conclusions Preoperative pulmonary function abnormality in patients before liver transplantation such as pulmonary ventilatory function reduction (VCmax ＜ 80% or FEV1.0 ＜ 80% ) and moderate to severe pulmonary diffusing capacity reduction (TLCOSB ＜ 60% ) predicts higher incidence of postoperative pulmonary complications.

Objective To evaluate the effect of high mobility group box 1 (HMGB1)/ cysteinyl aspartate specific proteinase (Caspase)-1/Gasdermin D (GSDMD) signaling axis-mediated hepatocyte pyroptosis on liver ischemia-reperfusion injury (IRI). Methods C57BL/6 mice were randomly divided into the sham operation group (Sham group), IRI 2 h group, IRI 6 h group, IRI 12 h group, glycyrrhizic acid (GA)+Sham group and GA+IRI 12 h group (n=8 in each group). AML12 cells were evenly divided into the Sham group, IRI 12 h group, GA+Sham group and GA+IRI 12 h group. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1β and IL-6 in each group were detected by enzyme-linked immune absorbent assay(ELISA). The messenger ribonucleic acid (mRNA) levels of IL-1β and IL-6 were detected by reverse transcription polymerase chain reaction(RT-PCR). The pathological score of liver ischemia and cell apoptosis were compared among all groups. The expression level of HMGB1 in the liver tissues of each group was determined by immunohistochemistry. The expression levels of HMGB1, Caspase-1 and GSDMD proteins in the mouse liver tissues and AML12 cells were measured by Western blot. Results Compared with the Sham group, the serum levels of ALT, AST, IL-1β and IL-6 and the relative expression levels of IL-1β and IL-6 mRNA in the liver tissues were all significantly up-regulated after IRI in each group (all P < 0.05), and showed significant time-dependent pattern along with the prolongation of reperfusion time. Compared with the Sham group, the pathological score of hepatic ischemia and the apoptosis rate of hepatocytes were significantly increased after IRI in each group (all P < 0.05). Immunohistochemical results showed that the expression level of HMGB1 in the liver tissues was significantly up-regulated after IRI, which showed an increasing trend along with the prolongation within the period of 2-12 h. Western blot showed that compared with the Sham group, the relative expression levels of HMGB1, Caspase-1 and GSDMD proteins in vivo and in vitro were up-regulated in the IRI 12 h group. The relative expression level of HMGB1 protein was significantly up-regulated, whereas those of Caspase-1 and GSDMD proteins were significantly down-regulated in the GA+IRI 12 h group compared with those in the IRI 12 h group (all P < 0.05). Conclusions Hepatocytes probably activate the Caspase-1/GSDMD signaling pathway by releasing HMGB1, thereby triggering hepatocyte pyroptosis and leading to liver IRI. Inhibition of extracellular release of HMGB1 by GA may mitigate liver IRI.

Objective To investigate the effect of nucleotide-binding oligomerization domaincontaining protein 1 (NOD1) on pyroptosis in hepatic ischemia-reperfusion injury.Methods An animal model of ischemia-reperfusion injury was established.Thirty healthy,male,and clean C57 BL mice were randomly divided into sham operation group (sham group) and ischemia-reperfusion group (IR,including 2 h,6 h,12 h,24 h subgroups),6 per group.Serum ALT and AST levels in each group were measured by blood biochemistry.HE staining and TUNEL were used to observe the pathological changes of liver and hepatocyte apoptosis.Immunohistochemistry was used to detect the expression and distribution of NOD1 in each group.Western blotting was used to detect NOD1,MM2,pro-Caspase-1 and active-Caspase-1 expression.NOD1 siRNA and empty control siRNA were transfected into AML12 cells,then the hypoxia/reoxygenation model was established and cells were collected to detect the expression of NOD1,AIM2 and active-Caspase-1.Results The ALT and AST levels in IR group were significantly higher than those in sham group,and peaked at IR 12-h subgroup (P＜0.05).HE staining showed that hepatic injury was the most severe at 12 h after reperfusion.TUNEL results showed that the number of apoptotic cells was the greated at 12 h after reperfusion.Western blotting showed that NOD1 protein expression was highest at 12 h after reperfusion.With the prolongation of reperfusion time,the expression of AIM2 and active-Caspase-1 gradually increased,and that of pro-Caspase-1 gradually decreased.The expression of NOD1,AIM2 and activeCaspase-1 decreased after transfection of NOD1 siRNA into AML12 cells.Conclusions NOD1 promotes liver ischemia-reperfusion injury,which may be related to NOD1 promoting liver injury by activating pyroptosis.

Acute kidney injury is a common complication after liver transplantation, which severely affects clinical prognosis of liver transplant recipients. Multiple factors before, during and after liver transplantation may cause kidney injury. If not properly treated, it may progress into chronic kidney diseases, which significantly increases postoperative fatality and negatively affects clinical efficacy of liver transplantation. Therefore, prevention, diagnosis and treatment of acute kidney injury after liver transplantation is a hot topic for clinicians. In this article, the definition, diagnosis, risk factors, prevention and treatment of acute kidney injury after liver transplantation were reviewed, and potential risk factors and related therapeutic strategies during different stages of acute kidney injury after liver transplantation were analyzed, aiming to lower the risk of acute kidney injury after liver transplantation and further improve clinical prognosis of liver transplant recipients by optimizing treatment regimens.

Objective To explore the value of endocervical curettage (ECC) in the detection of high-grade cervical squamous intraepithelial lesion (HSIL). Methods We retrospectively analyzed the clinical features and colposcopical characteristics of 678 female patients with complete clinical data. Results Among 678 cases, 391 cases were confirmed by cervical biopsy only and 7 cases by ECC only (57.67% vs. 1.03%, P < 0.001). ECC checked out 287 HSIL patients (42.33%, including cervical biopsy positive and negative cases) and cervical biopsy checked out 671 HSIL cases (98.97%, including ECC positive and negative cases). There were 68 positive ECC cases in the conversion area of Type 1+Type 2 and 247 positive ECC cases in the conversion area of Type 3(33.33% vs. 52.11%, P < 0.001). The positive rates of ECC in patients≥45 years old and < 45 years old were 145 and 170, respectively (55.13% vs. 40.96%, P < 0.001). Conclusion The cervical biopsy plays a dominant role in the detection of HSIL, and ECC can only be used as a supplement to it. Female patients older than 45 years or with Type 3 transformation zone examined by colposcopy should be concerned with cervical lesions.

Objective:To explore the role and molecular mechanism of DNAJB6 in liver regeneration during partial liver transplantation(PLT).Methods:Dark agouti(DA, donor)and Lewis(recipient)rats were prepared for liver regeneration model of PLT.Rats were divided into before perfusion, after split liver perfusion, after portal vein opening, before abdominal closure and Day 3/7 after surgery groups(n=6 each)for timepoints of PLT.C57 mice were performed for residual liver regeneration model of partial hepatectomy and divided into control, Day 1/2/3/4/5 groups(n=6 each)for timepoints of hepatectomy.Gene Expression Omnibus liver regeneration data were utilized for locating DNAJB6 in liver regeneration.DNAJB6 low-expression human hepatocytes were constructed by DNAJB6-Si transfection.The relationship between DNAJB6 and liver regeneration was examined by Western blot detection of cell proliferation markers PCNA and CCK8 cell proliferation experiments.And the possible molecular mechanism of DNAJB6 regulating liver regeneration in PLT was studied by Western blot detection of nuclear protein and protein in cell proliferation signal pathway.Results:The result of residual liver regeneration of partial hepatectomy showed that DNAJ family genes were differentially expressed on regenerated liver gene chip and DNAJB6 was lowly expressed on regenerated liver gene chip.Meanwhile, DNAJB6 was lowly expressed in regenerated liver tissues of PLT and partial liver resection.After silencing DNAJB6 by transfecting DNAJB6-Si, the cellular expression level of PCNA and proliferation rate increased.However, nuclear extraction failed to detect the nuclear/plasma changes of β-catenin and the level of Wnt4 protein had no obvious change.Although the activation levels of p38 and JNK2 downstream of Ras/MAPK showed no change, there was a higher activation level of ERK.Conclusions:In regenerating liver tissue, hepatocytes may suppress the Ras/MEK/ERK signaling pathway by lowering the expression level of DNAJB6 to promote liver regeneration.

Objective To evaluate the efficacy of in-situ split liver transplantation (ISSLT) in children.Methods From June 2015 to August 2018,10 liver grafts from DBD were split in-situ.All the donors were male,and the median age of the donors was 28.5 year old (18-48 year).One left half graft and 9 left lateral lobe grafts (including 2 reduced size grafts) were transplanted to 10 pediatric recipients.Four grafts were transplanted in our center,and the rest 6 grafts were shared to other two transplant center.The primary diseases of the recipients included biliary atresia (8/10),hepatic sinus obstruction syndrome (1/10) and Alagille syndrome (1/10).The median age of the recipients was 10 month (7 month-11 year),and the mean body weight was 9.8 ± 6.6 kg (5-28 kg).Results All liver grafts were split in-situ.The mean split time of liver grafts was 88.5 ± 18.9 min.The mean weight of split grafts was 336.7-± 85.4 g.All recipients were subjected to piggyback liver transplantation.Operation time was 542.5 ± 112.1 min.Anhepatic time was 52.0 ±-13.5 min.GRWR was (3.98 ±0.96)％.GRWR of two cases was more than 5％,so segment Ⅲ was partially reduced.During the follow-up period,9 cases were alive and 1 case died due to multiple organ failure 1 day after liver transplantation.Conclusions ISSLT can enlarge the graft pool for children and achieve good results.