[The effect of steatotic donor livers on the prognosis of donors and recipients after pediatric living donor liver transplantation].

Objectives: To evaluate the effects of steatotic donor livers on the safety of donors and the prognosis of donors and recipients in pediatric living donor liver transplantation. Methods: A total of 814 pediatric living donor liver transplantations were performed between January 2013 and December 2020 at Department of Pediatric Organ Transplantation,Tianjin First Central Hospital.The clinical data were collected and a retrospective study was conducted.The recipients and the donors were divided into non-steatotic donor liver group(n=733) and steatotic donor liver group(n=81) according to whether the donor graft had steatosis. The recipients and the donors in the steatotic donor liver group were further divided into mild and moderate steatosis groups based on the degree of liver steatosis.Among the donors of non-steatosis donor group,there were 307 males and 426 females,with a median age of 30 years(range:18 to 57 years);the recipients included 351 males and 382 females,with a median age of 7 months(range:4 month to 14 years).Among the donors of steatosis donor group,there were 41 males and 40 females,with a median age of 31 years(range:22 to 51 years);the recipients included 34 males and 47 females,with a median age of 8 months(range:5 months to 11 years).The donors and the recipients were followed up regularly by means of outpatient reexamination and questionnaire survey after operation.Statistical analysis of data between groups was performed using t-test,Wilcoxon rank-sum test,repeated measures ANOVA,χ2 test,or Fisher's exact test,respectively.The survival curves of recipients and grafts in different groups were created by Kaplan-Meier method,and the survival rates of the steatotic donor liver group and the non-steatotic donor liver group were compared by Log-rank method. Results: There was no significant difference in the gender of donors in both groups (P=0.132).There were significant differences in the age and blood type distribution as well as body weight and body mass index(all P<0.05) between the two groups.No significant difference was seen in the recovery of liver function markers ALT and AST at 1,2,5 days and 1 month after operation (all P>0.05) between the two groups.The steatotic donor liver group showed longer operation time ((294±75) minutes vs. (264±81) minutes; t=3.149,P=0.002),increased incidence of postoperative biliary leakage (3.7%(3/81) vs. 0.5% (4/733); P=0.025) and delayed incision healing (7.4%(6/81) vs. 2.0%(15/733); P=0.013).There were no significant differences in gender,age,blood type distribution,height,weight and pediatric end-stage liver disease score of recipients between the two groups (all P>0.05).As compared to the non-steatotic donor liver group,the steatotic donor liver group showed similar levels of ALT, AST and total bilirubin within 2 weeks after operation(all P>0.05). The cumulative recipient survival rates in both groups were both 96.3%,the cumulative graft survival rates were 96.3% and 95.5%,respectively,without significant difference(both P>0.05). No statistical difference was observed in the incidence of major complications between the two groups (all P>0.05). There was no significant difference in the recovery of liver function markers of donors and recipients between mild and moderate steatosis groups(all P>0.05).The cumulative recipient survival rates were both 95.9% and the cumulative graft survival rates were both 100% in mild and moderate steatosis groups,without significant difference(P=0.592). Conclusions: The application of mild to moderate steatotic donor livers in pediatric living donor liver transplantation may prolong the operation time of donors,increase the incidence of complications such as biliary leakage and delayed incision healing. But there is no significant impact of mild to moderate steatotic donor livers on the overall postoperative recovery of donors and recipients,and the prognosis is ideal.

[Risk factors of blood loss during liver transplantation in children with biliary atresia and its influence on prognosis].

Objectives: To study the risk factors for massive intraoperative blood loss in children with biliary atresia who underwent liver transplantation for the first time,and to analyze their impacts on graft survival,hospital stay and postoperative complications. Methods: The data of 613 children with biliary atresia who underwent liver transplantation at Department of Pediatric Organ Transplantation,Tianjin First Central Hospital from January 2015 to December 2018 were collected and analyzed. There were 270 males and 343 females, aged 7.4 (3.9) months (range: 3.2 to 148.4 months), the body weight of the recipients were (7.8±3.5) kg (range: 4.0 to 43.3 kg).According to the 85th quad of estimated blood loss(EBL),they were divided into two groups:massive EBL group(96 cases) and non massive EBL group(517 cases). The age,height,weight and other factors between the two groups were analyzed and compared. Univariate Logistic regression and multiple stepwise regression were used to determine the risk factors of massive EBL. Then,the postoperative complications of the two groups,including portal vein thrombosis and portal vein anastomotic stenosis etc.,were analyzed and compared by chi square test. Kaplan Meier curve and log rank test were used to analyze the recipient and graft survival rate of the two groups. Results: During the study period,713 transplants were performed and 613 patients were enrolled in the study. Ninety-six patients(15.7%) had massive EBL,and the postoperative hospital stay was 21(16) days(range:2 to 116 days),the hospital stay of non-massive EBL group was 22(12)days(range:3 to 138 days)(U=24 224.0,P=0.32). Univariate Logistic regression analysis showed that the recipient's weight,Kasai portoenterostomy,platelet count,operation time and cold ischemia time were the risk factors of massive EBL during biliary atresia transplantation. Multiple regression analysis showed that cold ischemia time ≥10 hours,prolonged operation time(≥8 hours) and body weight<5.5 kg were important independent risk factors for massive EBL.The incidence of portal vein thrombosis,hepatic vein stenosis,intestinal leakage and pulmonary infection in patients with massive EBL were significantly higher than those without massive EBL(3.1% vs. 0.8%,9.4% vs. 2.1%,6.3% vs. 0.8%,30.2% vs. 20.1%,all P<0.05). The 3-year overall graft and recipient survival rate were significantly lower in patients with massive EBL than those without massive EBL(87.5% vs. 95.7%,P=0.001;84.4% vs. 95.4%,P<0.01,respectively). Conclusions: In children with biliary atresia who underwent liver transplantation for the first time,the effective control of intraoperative bleeding should shorten the operation time and reduce the cold ischemia time as far as possible,on the premise of ensuring the safety of operation. For children without growth disorder,the weight of children should be increased to more than 5.5 kg as far as possible to receive the operation. Reducing intraoperative bleeding is of great significance to the prognosis of children.

[Clinical study of causes and outcomes in pediatric liver retransplantation].

Objective: To investigate the etiology,clinical features and prognosis of pediatric liver retransplantation. Methods: The data of 1 024 cases of pediatric liver transplantation (<18 years old) from January 2014 to December 2019 operated at Tianjin First Central Hospital were collected,retrospectively. Retransplantation was performed in 26 cases,among which 25 cases received secondary liver transplantation and 1 case received a third liver transplantation. There were 13 male and 12 female patients among the 25 patients. The median age was 12.9(20.5) months(range: 5.8 to 134.8 months), the body weight was 8.0(5.6) kg(range: 5.0 to 30.0 kg) at the time of retransplantation. The pediatric end-stage liver disease(PELD) score was 17.0(21.3) (range: 0 to 45) before retransplantation. The etiology of retransplantation was biliary complications in 7 cases,primary nonfunction of liver graft in 5 cases,antibody-mediated rejection in 4 cases,hepatic artery thrombosis in 3 cases,portal vein thrombosis in 3 cases,concomitant hepatic artery and portal vein thrombosis in 2 cases,thrombogenesis of inferior Vena Cava in 1 case and sinusoidal obstruction syndrome in 1 case. The patients were divided into two groups according to the time interval(30 days) between two liver transplantations,8 patients were classified into early-retransplantation(≤30 days) group and 18 patients were classified into late-retransplantation (>30 days) group. The etiology of liver retransplantation,pre-transplant score,time interval between two transplantations,surgical aspects,major complications and survival rates were compared between the two groups. Continuous variables with normal distribution were compared with t test,while Mann-Whitney U test was applied to compare variables without normal distribution. Categorical variables were compared with chi-square test. The survival curves were created by Kaplan-Meier method and compared by Log Rank test. Results: The median follow-up time was 26.8(30.2) months(range: 1 day to 85.7 months), and the incidence of retransplantation was 1.9%. In the early-retransplantation group,the duration of surgery was (439.8±151.0)minutes,the graft-to-recipient weight ratio was 5.0(1.8)%(range:3.6% to 6.1%),the main cause for retransplantation were primary nonfunction and vascular complications. In the late-retransplantation group,the duration of surgery was (604.4±158.0)minutes,the graft-to-recipient weight ratio was 3.4(2.1)%(range:1.4% to 5.3%),the main cause for retransplantation were biliary complications,antibody mediated rejection and vascular complications.The 3-month,1-year and 2-year recipient survival rates in the early-retransplantation group were all 62.3%,while the recipient survival rates in the late-retransplantation group were 100%,93.8% and 93.8%,respectively. The difference of recipient survival rates was significant between the early-retransplantation group and the late-retransplantation group(P=0.019). The overall 3-month,1-year and 3-year recipient survival rates after the primary liver transplantation were 97.1%,95.4%,94.1%,respectively. Conclusions: The vascular complications,biliary complications,primary nonfunction and antibody-mediated rejection are the main causes of liver retransplantation.The PELD score is higher in patients receiving early retransplantation,while the surgery is relatively more complex in patients receiving late retransplantation,which is reflected by longer duration of surgeries. Patients in the late-retransplantation group showed similar recipient survival rates with primary liver transplantation recipients,and the survival rates are superior to those of patients in the early-retransplantation group. Infection and multiple organ failure are the most common fatal causes after retransplantation.

[Insight and judgment on recurrence of hepatocellular carcinoma after liver transplantation].

Hepatocellular carcinoma (HCC) is the most important cause of adult liver transplantation in China. HCC recurrence after liver transplantation is a common clinical problem. It is imperative to explore its metastasis and recurrence mechanism and to develop effective prevention and treatment strategies. This article describes the basic prevention and treatment strategies for recurrent HCC after liver transplantation. During the pre-transplant period, the clinical and pathological information of HCC, such as tumor staging, general morphology, pathological features, tumor markers and tumor molecular biological characteristics, should be collected and analyzed carefully in order to determine the risk of recurrent HCC; Design and implement a comprehensive program of prevention and treatment. Currently, sorafenib and capecitabine are common candidate drugs for prevention and control of recurrence of HCC after liver transplantation. Substitution of m-TOR inhibitors for CNI-like drugs can be used as an immunosuppressive drug to prevent and control recurrence of HCC. HCC recurrence after liver transplantation will significantly reduce the cure rate, but active treatment often can effectively control the progression of the disease and improve the prognosis. However, available effective measures to prevent the progress of HCC can also be used to treat HCC recurrence after liver transplantation. Surgical treatment is preferred for recurrent lesions that can be resected, and local treatment is available for recurrent lesions that cannot be resected. Drug treatment can inhibit tumor growth to a certain extent, but it is difficult to achieve a satisfying prognosis by single drug, commonly used as adjuvant therapy.

Synonymous codon usage patterns in different parasitic platyhelminth mitochondrial genomes.

We analyzed synonymous codon usage patterns of the mitochondrial genomes of 43 parasitic platyhelminth species. The relative synonymous codon usage, the effective number of codons (NC) and the frequency of G+C at the third synonymously variable coding position were calculated. Correspondence analysis was used to determine the major variation trends shaping the codon usage patterns. Among the mitochondrial genomes of 19 trematode species, the GC content of third codon positions varied from 0.151 to 0.592, with a mean of 0.295 ± 0.116. In cestodes, the mean GC content of third codon positions was 0.254 ± 0.044. A comparison of the nucleotide composition at 4-fold synonymous sites revealed that, on average, there was a greater abundance of codons ending on U (51.9%) or A (22.7%) than on C (6.3%) or G (19.14%). Twenty-two codons, including UUU, UUA and UUG, were frequently used. In the NC-plot, most of points were distributed well below or around the expected NC curve. In addition to compositional constraints, the degree of hydrophobicity and the aromatic amino acids also influenced codon usage in the mitochondrial genomes of these 43 parasitic platyhelminth species.

Dihydroayapin, a new coumarin compound from Dendrobium densiflorum.

A new coumarin named dihydroayapin (1) together with seven known compounds were isolated from the stems of Dendrobium densiflorum. On the basis of physicochemical and spectral evidences, the structure of 1 was established as 6,7-methylenedioxy-3,4-dihydrobenzopyran-2-one.

Beta-adrenoceptor subtype activities of trimetoquinol derivatives: biochemical studies on human beta-adrenoceptors expressed in chinese hamster ovary cells.

The beta-adrenoceptor activities of trimetoquinol (TMQ) isomers and selected derivatives were evaluated on human beta-adrenoceptor subtypes expressed in Chinese hamster ovary cells. In cAMP accumulation assays, (-)-TMQ was 214-, 281-, and 776-fold more potent than (+)-TMQ at stimulating beta(1)-, beta(2)-, and beta(3)-adrenoceptor subtypes, respectively. In radioligand binding assays, (-)-TMQ exhibited 123-, 331-, and 5-fold greater affinity than (+)-TMQ for beta(1)-, beta(2)-, and beta(3)-adrenoceptor subtypes, respectively. (-)-TMQ and (+/-)-TMQ activated the human beta(3)-adrenoceptor with an 8.2- and 3.4-fold greater efficacy, respectively, than the reference beta-adrenoceptor agonist (-)-isoproterenol (efficacy = 1). The 3',5'-diiodo analogs of TMQ were partial agonists of the beta(2)-adrenoceptor relative to (-)-isoproterenol, and their potencies were 5- to 10-fold higher at the beta(3)-adrenoceptor as compared with beta(1)-adrenoceptors. Modification of the catechol (6,7-dihydroxy) nucleus, such as replacement of the 7-hydroxy group with a chloro group (7-chloroTMQ), ring fluorination (8-fluoro and 5,8-difluoro analogs), or preparation of bioisosteric tetrahydrothiazolopyridine (THP) derivatives of TMQ yielded compounds that displayed partial agonist activity (relative to (-)-isoproterenol) or were inactive at the beta(2)-adrenoceptor and exhibited beta(3)-adrenoceptor-selective stimulation compared with the beta(1)-adrenoceptor. Furthermore, the 3',5'-diiodo-4'-methoxybenzylTHP derivative of TMQ was 65-fold more potent than the corresponding 3',4',5'-trimethoxybenzylTHP at the human beta(3)-adrenoceptor. Our results indicate that 6, 7-dihydroxy-catechol-modified and 1-benzyl halogen-substituted derivatives of TMQ represent promising leads for the development of beta(3)-adrenoceptor-selective agonists.

Murine NK cell allospecificity-1 is defined by inhibitory ligands.

Hemopoietic allografts of normal and neoplastic origin are subject to NK cell-mediated resistance in mice. Susceptibility to this resistance is controlled by MHC-linked genes in a recessive manner. Several distinct specificities could be postulated to explain the strain-dependent pattern of resistance. These presumptive specificities for recognition are H-2 haplotype dependent, but the correspondence is not one-to-one. For example, resistance of H-2d or H-2b/d host to H-2 b graft operationally defines specificity-1, establishing its link with haplotype H-2b. To examine the molecular basis of specificity-1, spontaneous Dd-loss mutant clones were isolated from H-2b/d and H-2d hemopoietic cell lines, i.e., 416B of (C57BL/6 x DBA/2)F1 (B6D2F1) origin and L1210 of DBA/2 origin, both of which lack specificity-1. The expression of specificity-1 in the mutant clones was examined in vivo and in vitro. The results indicate that Dd-loss clones of 416B and L1210 lines express specificity-1. These data suggest that murine NK cell allospecificity-1 is defined primarily by the absence of the Dd molecule or other class I molecules sharing the protective motifs; no H-2b-associated genes play a relevant role. This conclusion is consistent with the missing self hypothesis of NK cell reactivity, and is in agreement with the observation that lysis of B6 targets by B6D2F1 NK cells is mediated mostly by cells that express Ly-49A and/or Ly-49G2.

[Pulmonary encephalopathy and disturbance in amino acids metabolism].

18 kinds of serum free amino acids (SFAAs) were determined in 35 patients suffering from cor pulmonale (CP) with acute exacerbation of chronic obstructive pulmonary disease (COPD). We found that the branched-chain AAs/aromatic AAs ratio (BCAAs/AAAs) was smaller in patients with pulmonary encephalopathy (PE) than those with respiratory failure (RF) only. For the PE patients, this ratio was still smaller during unconscious period than during conscious period. Some SFAAs related to neurotransmitters were also altered during unconscious period. However, there was no significant difference between CP patients with simple RF and those without RF. When RF was controlled, the SFAAs remained unchanged. The above results suggested that disturbance in neutral AAs metabolism participates in the mechanism of PE formation.