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Objective:To investigate the influencing of high sodium donor liver transplan-tation from the death of a citizen′s organ donation (DCD) on the prognosis of recipients.Methods:The retrospective cohort study was constructed. The clinicopathological data of 125 pairs of donors and recipients who underwent DCD liver transplantation in Xijing Hospital of Air Force Military Medical University from January 2015 to June 2021 were collected. Of the 125 donors, there were 93 males and 32 females. Of the 125 recipients, there were 92 males and 33 females, aged 48(41,55)years. According to the last time of serum sodium level of donor liver in the 125 recipients, 9 donor livers with serum sodium level ≥170 mmol/L were divided into group 1 (extremely high sodium), 33 donor livers with serum sodium level ≥150 mmol/L and <170 mmol/L were divided into group 2 (moderate high sodium), and 83 donor livers with serum sodium level <150 mmol/L were divided into group 3 (normal sodium), respectively. Observation indicators: (1) postoperative recover situations; (2) follow-up and survival analysis. Measurement data with normal distribution were represented as Mean± SD. Repeated measures were analyzed by repeated measures ANOVA. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Kruskal-Wallis test. Count data were described as absolute numbers, and Pearson chi-square test or Fisher exact probability were used for data test. The Kaplan-Meier method was used to draw survival curves and Log-rank test was used for survival analysis. Results:(1) Postoperative recover situations. The changes of alanine transaminase (AlT), aspartate aminotransferases (AST), total bilirubin (TBil), alkaline phosphatase (ALP), prothrombin time (PT), international normalized ratio (INR), albumin (Alb) and creatinine (Cr) from the first day to the 14th day after operation were (736±972)IU/L to (75±46)IU/L, (1 290±1 651)IU/L to (38±20)IU/L, (102±98)μmol/L to (33±11)μmol/L, (66±34)IU/L to (104±54)IU/L, (19.9±3.3)seconds to (11.3±1.0)seconds, 1.76±0.31 to 1.00±0.08, (34±5)g/L to (38±3)g/L and (91±41)μmol/L to (76±19)μmol/L, respectively, in the recipients of group 1. The above indicators were (505±377)IU/L to (48±46)IU/L, (855±727)IU/L to (24±17)IU/L, (64±42)μmol/L to (32±22)μmol/L, (68±51)IU/L to (91±46)IU/L, (16.8±3.5)seconds to (11.9±1.2)seconds, 1.47±0.30 to 1.04±0.09, (33±4 g/L) to (40±5)g/L and (106±32)μmol/L to (97±27)μmol/L in the recipients of group 2 and (637±525)IU/L to (65±60)IU/L, (929±1 193)IU/L to (33±27)IU/L, (66±48)μmol/L to (33±36)μmol/L, (64±28)IU/L to (125±64)IU/L, (17.2±4.7)seconds to (13.3±12.8)seconds, 1.51±0.42 to 1.05±0.13, (35±6)g/L to (39±4)g/L, (105±44)μmol/L to (94±40)μmol/L in the recipients of groups. Results of overall effect showed there were significant differ-ences in the change trend of TBil (time effect, inter-group effect, interaction effect) in recipients among the three groups after liver transplantation ( Fgroup=5.42, Ftime=22.78, Finteraction=3.85, P<0.05). There were significant differences in the time effect of ALT, AST, ALP, PT, INR, Alb, Cr in recipients among the three groups after liver transplantation ( Ftime=50.17, 36.24, 19.24, 10.55, 59.61, 41.94, 10.82, P<0.05). (2) Follow-up and survival analysis. All recipients were followed up. Cases with early postoperative liver dysfunction, cases with donor liver failure 1 year after operation, cases with biliary complica-tions 1 year after operation, cases with vascular complications 1 year after operation, cases with rejection 1 year after operation were 2, 1, 0, 0, 0 in the recipients of group 1. The above indicators were 2, 1, 3, 0, 1 in the recipients of group 2 and 10, 8,20, 1, 6 in the recipients of group 3. There was no significant difference in the above indicators among the three groups ( χ2=1.58, 0.60, 5.19, 1.62, 0.97, P>0.05). The 1-year and 3-year cumulative survival rates of the donor liver were 100.00% and 100.00% in the recipients of group 1 after liver transplantation. The above indicators were 94.74% and 77.16% in the recipients of group 2 and 91.57% and 89.30% in the recipients of group 3. There was no significant difference in the cumulative survival rate of donor liver among the three groups ( χ2=2.69, P>0.05). The 1-year and 3-year cumulative survival rates were 100.00% and 100.00% in the recipients of group 1 after liver transplantation. The above indicators were 93.74% and 77.16% in the recipients of group 2 and 89.40% and 86.00% in the recipients of group 3. There was no significant difference in the cumulative survival rate among the three groups ( χ2=1.94, P>0.05). Conclusion:Donor livers with high serum sodium level can be used in the DCD liver transplantation.
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Objective To evaluate the role and potential mechanism of interleukin (IL)-18/IL-18 binding protein (BP) in mediating the killing effect of natural killer (NK)-92MI cells upon endothelial cells from α-1, 3- galactosyltransferase gene-knockout (GTKO) porcine models. Methods NK-92MI cells were divided into the NK, NK+IL-18, NK+GTKO, IL-18+NK+GTKO and IL-18+IL-18BP+NK+GTKO groups. The messenger ribonucleic acid (mRNA) levels of inflammation-related genes in NK-92MI cells were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The killing effect of NK-92MI cells on endothelial cells from GTKO porcine models was evaluated by lactate dehydrogenase (LDH) assay. The apoptosis of endothelial cells from GTKO porcine models was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The expression levels of proteins with killing effect and apoptosis-related proteins were determined by Western blot. Results Compared with the NK, NK+IL-18 and NK+GTKO groups, the expression levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-8, IL-3, IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA were up-regulated in NK-92MI cells in the IL-18+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the IL-18+NK+GTKO group, the expression levels of IFN-γ, TNF-α, IL-8, IL-3, IL-6 and GM-CSF mRNA were down-regulated in NK-92MI cells in the IL-18+IL-18BP+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the NK+GTKO group, the expression levels of perforin, granzyme B and IFN-γ proteins in NK-92MI cells were up-regulated, the killing rate of NK-92MI cells against endothelial cells from GTKO porcine models was enhanced, the apoptosis rate of endothelial cells from GTKO porcine models was increased, and the ratios of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/Bcl-2 and cleaved Caspase-3/Caspase-3 in endothelial cells from GTKO porcine models were elevated in the IL-18+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the IL-18+NK+GTKO group, the expression levels of perforin, granzyme B and IFN-γ proteins were down-regulated, the killing rate of NK-92MI cells against endothelial cells from GTKO porcine models was decreased, the apoptosis rate of endothelial cells from GTKO porcine models was decreased, and the ratios of Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 in endothelial cells from GTKO porcine models were declined in the IL-18+IL-18BP+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Conclusions IL-18BP may block the expression of inflammation-related genes in NK-92MI cells induced by IL-18 and the killing effect of NK-92MI cells on endothelial cells from GTKO porcine models.
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Objective:To investigate the influencing factors for hepatic artery complica-tions of liver transplantation from donation after citizen's death.Methods:The retrospective cohort study was conducted. The clinicopathological data of 147 recipients who underwent liver transplan-tation from donation after citizen's death in Xijing Hospital of Air Force Military Medical University from January 2015 to June 2020 were collected. There were 109 males and 38 females, aged (46±12)years. All recipients underwent liver transplantation from donation after citizen's death. Observation indicators: (1) surgical situations; (2) occurrence of hepatic artery complications after liver transplantation; (3) analysis of donor related influencing factors for hepatic artery complications after liver transplantation; (4) analysis of recipient related influencing factors for hepatic artery complications after liver transplantation; (5) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect survival of recipients up to June 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Univariate analysis was conducted using the Fisher exact probability, and multivariate analysis was conducted using the COX regression model. Kaplan-Meier method was used to calculate the cumulative survival rate and draw the survival curve. Results:(1) Surgical situations: of the 147 recipients, 108 cases underwent orthotopic liver transplantation, and 39 cases underwent piggyback liver transplantation. The operation time of 147 recipients was (458±101)minutes. (2) Occurrence of hepatic artery complications after liver transplantation: 4 of the 147 recipients had hepatic artery complications, including 3 cases with hepatic artery embolism and 1 case with hepatic artery stenosis. The time to occurrence of hepatic artery complications after liver transplantation was (5±2)days. (3) Analysis of donor related influencing factors for hepatic artery complications after liver transplantation: results of univariate analysis showed that age, atherosclerosis, fatty liver and arterial variation were not donor related factors influencing hepatic artery complications after liver transplantation ( P>0.05). (4) Analysis of recipient related influencing factors for hepatic artery complications after liver transplantation: results of multivariate analysis showed that insufficient hepatic artery blood flow in the recipient was an independent risk factor for hepatic artery complications after liver transplantation ( hazard ratio=10.13, 95% confidence interval as 1.05-97.42, P<0.05). (5) Follow-up: 146 of the 147 recipients were followed up for 1 to 77 months, with a median follow-up time of 34 months. The 1-year cumulative survival rate of the 146 recipients was 92.2%. Conclusion:Insufficient hepatic artery blood flow of the recipient is an independent risk factor for hepatic artery complications after liver transplantation from donation after citizen's death.
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Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.
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It is proven that laparoscopic sleeve gastrectomy (LSG) is effective for obesity, type 2 diabetes mellitus and other obesity-related complications. The surgical procedure of LSG is relatively simple, with few short-term or long-term complications, which has increasing be applicated in recent years. As more hospitals in China carry out LSG, the related reports of its complications have gradually increased. The most common complications of LSG include gastric leakage, bleeding, and gastric cavity stenosis. Among them, gastric leakage is a more difficult problem, and untreated or improper treatment can bring serious consequences to patients. Based on the current progress in clinical treatment of gastric leakage after LSG and practical experience, the authors summarize and discusse the clinical experience of the prevention and treatment of such patients.
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Objective To evaluate the effect of hypernatremia in donors on perioperative recovery of liver function in the recipients undergoing liver transplantation. Methods Clinical data of 73 liver transplant recipients were analyzed retrospectively. According to the serum levels of sodium in donors, all recipients were divided into hypernatremia group (donor serum sodium ≥150 mmol/L, n=19) and non-hypernatremia group (donor serum sodium < 150 mmol/L, n=54). Serum alanine aminotransferase(ALT), aspartate aminotransferase (AST), model for end-stage liver disease (MELD) score, albumin, total bilirubin (TB), serum creatinine, prothrombin time and hepatocyte growth factor (HGF) in the recipients were detected at 1, 3, 7, 14 and 21 d after liver transplantation. The time of postoperative use of liver-protecting drugs in the recipients, the length of intensive care unit (ICU) stay, the average length of hospital stay and the incidence rate of postoperative complications were statistically compared and analyzed. Results Compared with the non-hypernatremia group, the serum levels of TB, ALT, AST, HGF and MELD scores of the recipients in the hypernatremia group at the postoperative 1, 3 and 7 d were significantly higher (all P < 0.05), whereas the serum albumin level was significantly decreased (P < 0.05). The prothrombin time in the hypernatremia group was significantly longer than that in the non-hypernatremia group at 3 and 7 d after operation (both P < 0.05). In the hypernatremia group, the time of postoperative use of liver-protecting drugs and the length of ICU stay were 9 (7-13) d and 11 (8-13) d, significantly longer than 4 (3-9) d and 7 (3-9) d in the non-hypernatremia group (both P < 0.05). The average length of hospital stay, serum creatinine level and incidence rate of postoperative complications did not significantly differ between two groups (all P>0.05). All recipients were recovered and discharged. Conclusions The hypernatremia in donors exert no significant effect on the perioperative liver function of the recipients, whereas it can prolong the postoperative recovery time of liver function of the recipients.
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Objective@#To explore the therapeutic feasibility of uterus transplantation for uterine infertility.@*Methods@#Retrospective analysis was performed for the diagnosis, treatment and pregnancy course of the first domestic case of uterus transplantation and the relevant literature reviewed. The recipient was a 22-year-old woman with a congenital absence of uterus and vagina. Previously she underwent vaginal reconstruction and the donor was her mother. The specific procedures included donor/recipient screening, ethical argumentation, assisted reproductive technology of obtaining frozen embryos, Vinci robot-assisted uterine procurement, orthotopic replacement & fixation of retrieved uterus, revascularization; immunoregulation & monitoring of transplanted uterine recipient, assisted reproductive technology after transplantation and gestational management.@*Results@#The durations of donor and recipient surgeries were 360 and 530 min respectively. No complications of recipient or donor occurred during the perioperative period. First menstruation occurred at 40 days post-transplantation and regularly thereafter. Pregnancy occurred after embryo transfer at 31 months post-transplantation. No rejection episodes occurred after transplantation or during gestation. Caesarean delivery occurred near gestational week 34. The boy weighed 2000 grams at birth and the mother remained well.@*Conclusions@#In conjunctions with literature review, uterine infertility may be treated by modified uterus transplantation. And a new path is paved for healthy pregnancy of women with uterine infertility.
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Objective To explore the therapeutic feasibility of uterus transplantation for uterine infertility .Methods Retrospective analysis was performed for the diagnosis ,treatment and pregnancy course of the first domestic case of uterus transplantation and the relevant literature reviewed .The recipient was a 22-year-old woman with a congenital absence of uterus and vagina .Previously she underwent vaginal reconstruction and the donor was her mother . The specific procedures included donor/recipient screening , ethical argumentation ,assisted reproductive technology of obtaining frozen embryos , Vinci robot-assisted uterine procurement ,orthotopic replacement & fixation of retrieved uterus , revascularization;immunoregulation &monitoring of transplanted uterine recipient , assisted reproductive technology after transplantation and gestational management .Results The durations of donor and recipient surgeries were 360 and 530 min respectively .No complications of recipient or donor occurred during the perioperative period .First menstruation occurred at 40 days post-transplantation and regularly thereafter .Pregnancy occurred after embryo transfer at 31 months post-transplantation .No rejection episodes occurred after transplantation or during gestation .Caesarean delivery occurred near gestational week 34 .The boy weighed 2000 grams at birth and the mother remained well . Conclusions In conjunctions with literature review , uterine infertility may be treated by modified uterus transplantation .And a new path is paved for healthy pregnancy of women with uterine infertility .
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Liver transplantation is the only effective method for the treatment of end-stage liver disease, but there are still controversies over its application in the treatment of intrahepatic cholangiocarcinoma (ICC). ICC has a high degree of malignancy, occult symptoms, and a lack of specific clinical manifestations in the early stage. Most patients are in the advanced stage at the time of diagnosis and lose the opportunity for surgical resection, and thus they tend to have poor prognosis. With the research advances in liver transplantation for the treatment of ICC, development of standardized criteria for patient selection and combination with neoadjuvant therapy and adjuvant therapy may become a promising method for the treatment of locally advanced ICC.
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Objective To investigate the mechanism underlying the activation of tissue factor (TF) that leads to coagulation dysfunction in the recipients after liver xenotransplantation. Methods Auxiliary heterotopic liver xenotransplantation was performed in 3 minipigs with α-1,3-galactosyltransferase gene-knockout (GTKO) as the donors and Tibetan macaque (Macaca thibetana) as the recipients. Postoperative coagulation function changes in the recipients were observed. Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were adopted to quantitatively measure the expression levels of monkey and minipig TF messenger RNA (mRNA) and protein in the liver tissues of the primary and transplant livers at different time points before and after transplantation. The recalcification time of peripheral blood mononuclear cell (PBMC) was recorded in the normal control monkeys and the recipient monkeys before and 2 h after liver transplantation to evaluate the coagulation status in the recipients. Results All three recipients presented with different degrees of coagulation dysfunction after surgery, manifested as a decrease in fibrinogen level and a reduction in platelet count. The monkey TF protein was positively expressed in the primary livers after surgery, whereas negatively expressed in transplant livers before and after liver transplantation. The minipig TF protein was negatively expressed in both primary livers and transplant livers. At postoperative 2 h, monkey TF mRNA was up-regulated by (2.10±0.24) times in the primary liver compared with the preoperative level, whereas the minipig TF mRNA was up-regulated by (1.42±0.15) times compared with preoperative level. There was statistical significance between the primary livers and transplant livers (P=0.014). Compared with PBMC in the normal control monkeys and recipient monkeys before liver transplantation, the recalcification time of the PBMC in the recipient monkeys was significantly shortened at postoperative 2 h (both P<0.001). Conclusions At the presence of coagulation dysfunction after liver xenotransplantation, the level of TF activation in the primary livers is significantly higher than that in the transplant livers. The TF activation in the primary livers is the main cause of coagulation dysfunction after liver xenotransplantation.
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Liver cancer is a malignant tumor with the characteristics of high morbidity and mortality.However,the routine detection methods for the liver cancer such as imaging tests and pathological detection are with low specificity and sensitivity.And it's also hard to detect the condition of patients dynamically.Cell-free DNA (cfDNA) is the DNA fragment that is away from the extracellular and exists in the blood,which contains genetic information from the organism.The related disease information could be reflected on the cfDNA in patients with liver cancer,indicating that cfDNA has great potential in the screening,diagnosis,treatment and prognosis of liver cancer.The clinical applications of cfDNA can make up for the deficiency of existing detection methods and achieve noninvasive and dynamic monitoring of liver cancer.This article will present a review on the progress of clinical applications of cfDNA in liver cancer.
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Objective To investigate the protective roles of Epigallocatechin gallate (EGCG) on liver ischemia reperfusion injury (IRI) in rats.Methods 30 healthy male SD rats were selected and equally and randomly divided into 3 groups.Sham group,IRI group and IRI-EGCG group were established to construct 70％ liver IRI rat model.Drinking water with 0.4 mg/ml EGCG was administered for 2 weeks before the experiment in IRI-EGCG group.HE staining was performed to evaluate the injury.Transaminases in serum were investigated to assess liver injury.p-p85 and p-AKT was detected by Western-blot assay.qPCR was carried out to study the mRNA expression of TNF-α,IL-6 and IL-1β in liver tissue.The secretion of TNF-α,IL-6 and IL-1 β in serum was examined with ELISA assay.Results EGCG pretreatment reduced ASTand ALT in serum [AST:(550.0 ±66.5) IU/L vs.(220.0 ±63.5) IU/L;ALT:(376.0 ± 25.7) IU/L vs.(158.0 ± 33.1) IU/L,all P ＜ 0.05] and mitigated liver tissue damage.p-p85 and p-AKT increased due to liver IRI,and IRI-EGCG group showed higher expression of p85 and AKT.The proinflammatory cytokines of TNF-α,IL-6 and IL-1 β exhibited a relatively lower mRNA expression in IRI-EGCG group comparing with IRI group.IRI-EGCG group also revealed a decreased secretion of TNF-α,IL-6 and IL-1β in serum [TNF-α:(398.0±33.4) ng/Lvs.(211.0±23.6) ng/L;IL-6:(341.0±27.3) ng/L vs.(187.0±19.6) ng/L;IL-1β:(486.0±43.7) ng/L vs.(352.0±31.5) ng/L;allP＜0.05].Conclusion EGCG pretreatment can enhance IRI-induced activation of PI3K/AKT signaling and reduce the release of proinflammatory cytokines to exert liver protective effects.
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Objective To investigate the effect of microvascular invasion (MVI) on tumor recurrence of hepatocellular carcinoma (HCC) patients after hepatectomy,the efficacy of sequential transcatheter arterial chemoembolization (TACE) on positive MVI patients after hepatectomy,and the effect of comprehensive treatment on the prognosis of patients with tumor recurrence.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 136 HCC patients who underwent hepatectomy in the First Affiliated Hospital of Air Force Medical University from February 2015 to December 2016 were collected.Patients were treated with TACE,radiofrequency ablation (RFA) and molecular-targeted drugs after hepatectomy,and patients with tumor recurrence selected 1 or 2 above treatments.The patient received postoperatively outpatient reexaminations every 3 months to detect tumor recurrence and survival.Follow-up was from the day of the surgery to death or December 2017.Observation indicators:(1) treatment after hepatectomy;(2) effect of MVI on tumor recurrence of HCC patients after hepatectomy:clinicopathological features and tumor recurrence rate between positive and negative MVI patients;(3) efficacy of TACE on positive MVI patients:clinicopathological features and tumor recurrence rate in positive MVI patients with or without TACE;(4) effect of comprehensive treatment on the prognosis of patients with tumor recurrence.Measurement data with normal distribution were represented as x±s and analyzed using the independent-samples t test.Comparisons of count data were analyzed using chi-square test or Fisher exact probalility.The tumor recurrence rate and survival rate were calculated by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) Treatment after hepateetony:of 136 patients undergoing hepatectomy,117 underwent single hepatectomy and 19 combined sequential TACE;59 had HCC recurrence,including 22 receiving comprehensive treatment.(2) Effect of MVI on tumor recurrence of HCC patients after hepatectomy:① Clinicopathological features:of 117 patients undergoing single hepatectomy,positive MVI was detected in 49 patients,including 44 males and 5 females,with an age of (52-± 10)years old;49 patients were in Child-Pugh grade A,including 36 combined with liver cirrhosis and 13 without liver cirrhosis;positive and negative alpha-fetoproteins (AFPs) were respectively detected in 34 and 15 patients.Negative MVI was detected in 68 patients,including 54 males and 14 females,with an age of (55± 11)years old;65 and 3 patients were respectively in Child-Pugh grade A and B,including 52 combined with liver cirrhosis and 16 without liver cirrhosis;positive and negative AFPs were respectively detected in 39 and 29 patients.There was no statistically significant difference in gender,age,Child-Pugh score of liver function,liver cirrhosis and comparison of AFP between positive and negative MVI patients (x2 =2.258,t =-1.626,x2 ＝ 0.804,0.138,1.758,P＞0.05).② Tumor recurrence rate:The 6-month and 1-year tumor recurrence rates after hepatectomy were respectively 30.77％,30.61％ in 117 patients undergoing single hepatectomy and 42.86％,51.02％ in 49 of 117 patients with positive MVI and 22.06％,27.94％ in 68 of 117 patients with negative MVI,showing statistically significant differences in 6-month and 1-year tumor recurrence rates between positive and negative MVI patients (x2 =5.738,6.465,P＜0.05).(3) Efficacy of TACE on positive MVI patients:① Clinicopathological features of 56 patients with positive MVI,7 received postoperatively sequential TACE,including 7 males,with an age of (50±4) years old;56 patients were in Child-Pugh grade A,including 5 combined with liver cirrhosis and 2 without liver cirrhosis;positive and negative AFPs were respectively detected in 2 and 5 patients.Forty-nine patients didn't combine sequential TACE,including 44 males and 5 females,with an age of (52± 10)years old;49 patients were in Child-Pugh grade A,including 36 combined with liver cirrhosis and 13 without liver cirrhosis;positive and negative AFPs were respectively detected in 34 and 15 patients.There was no statistically significant difference in gender,age,Child-Pugh score of liver function,liver cirrhosis and comparison of AFP between patients with and without sequential TACE (x2 =0.784,t =-0.512,x2 =0.013,2.844,P＞0.05).② Tumor recurrence:the 6-month and 1-year tumor recurrence rates after hepatectomy were respectively 0,28.57％ in 7 positive MVI patients with sequential TACE and 42.86％,51.02％ in 49 positive MVI patients without sequential TACE,showing a statistically significant difference in 6-month tumor recurrence rate (x2=4.800,P＜0.05) and no statistically significant difference in 1-year tumor recurrence rate (x2 =1.236,P ＞ 0.05).(4) Effect of comprehensive treatment on the prognosis of patients with tumor recurrence:of 59 patients with tumor recurrence,37 didn't receive comprehensive treatment,34 of 37 died within 1-year postoperatively,including 30 deaths within 6-month postoperatively,and 1-year survival rate was 8.10％;22 received comprehensive treatment,including 4 deaths within 1-year postoperatively,and 1-year survival rate was 81.80％,showing a statistically significant difference in 1-year survival rate (x2=32.698,P＜0.05).Conclusions MVI is one of the important risk factors affecting HCC recurrence and metastasis after hepatectomy.The combined TACE after hepatectomy can reduce the HCC recurrence rate of MVI positive patients,and active comprehensive treatment after HCC recurrence can significantly prolong the survival time of patients.
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To investigate the changes in the expression levels of scavenger receptor class B member 1 (SCARB 1) in the liver tissues before and after liver xenotransplantation and analyze the relationship between the variations in the SCARB1 expression and coagulation regulating dysfunction in the recipients.Methods The Wuzhishan miniature pig with α-1,3-galactosyltransferase gene-knockout(GTKO) was utilized as the donor and Macaca thibetana was chosen as the recipient.Heterotopic auxiliary liver xenotransplantation models were established.The liver tissue specimen was collected before and after liver xenotransplantation.Primary hepatocytes were extracted from the pig using collagenase digestion method.Human peripheral blood mononuclear cells were obtained by immunomagnetic bead sorting.These two types of cells were co-cultured and supplemented with human plasma to establish cell models with coagulation regulating dysfunction following liver xenotransplantation.Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were performed to quantitatively measure and statistically compared the expression levels of messenger ribonucleic acid (mRNA) and protein of SCARB1 in the tissue and cell samples.At the cellular level,the expression of SCARB 1 was interfered by lentiviral vector.The coagulation time was detected to validate the effect upon coagulation function.Results The expression levels of SCARB1 mRNA and protein were significantly down-regulated after liver xenotransplantation (both P＜0.05).In the cell models,the expression levels of SCARB1 mRNA and protein in the porcine hepatocytes co-cultured with human monocytes were significantly down-regulated compared with those in porcine hepatocytes without intervention (both P＜0.05).Compared with the non-intervention group,the coagulation time was significantly prolonged after the expression of SCARB1 was interfered by lentiviral vector (P＜0.05).Conclusions The down-regulated expression of SCARB1 in the liver graft is one of the main causes of mediating coagulation regulating dysfunction.Intervention of SCARB1 expression contributes to resolve the coagulation regulating dysfunction in the recipients after liver xenotransplantation.
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Objective To observe the reception of using pig bone marrow stromal cells (BMSCs) that were transfected with human tissue factor pathway inhibitor (TFPI) to resolve the dysregulation of coagulation after liver xenotransplantation.Methods Pig BMSCs were immortalized by transfection with lentivirus containing SV40T and then transfection with human TFPI.At last the cells were tested for their ability to inhibit clotting in a model by co-incubation of human plasma,human monocytes and pig aortic endothelial cells.Results After transfection with SV40T,pig BMSCs were immortalized and similar to primary cells.The immortalized pig BMSCs showed a stable TFPI expression after transfection with human TFPI by lentivirus.Moreover,they showed the potential of regulating coagulation dysregulation in vitro.Conclusion Pig BMSCs transfected with human TFPI could solve the regulation dysregulation caused by TF activation effectively,and have the potential of resolving coagulation dysregulation in liver xenotransplantation.
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Objective To investigate the clinical effects of laparoscopic sleeve gastrectomy with duodenaljejunal bypass (LSG + DJB) for the treatment of type 2 diabetes mellitus.Methods The clinical data of 17 patients with type 2 diabetes mellitus who underwent LSG + DJB at the Xijing Hospital of the Fourth Military Medical University from March 2013 to February 2014 were retrospectively analyzed.The fasting blood glucose,postprandial 2-hour blood glucose,glycosylated hemoglobin (HbA1c) and body mass index (BMI) in 17 patients before operation were (9.2 ± 0.6) mmol/L,(14.4 ± 2.2) mmol/L,8.3％ ± 1.2％ and (29.4 ± 2.2) kg/m2,respectively.All the patients received LSG + DJB and were followed up by outpatient examination up to March 2015.The pre-and post-operative 12-month fasting blood glucose,postprandial 2-hour blood glucose,HbA1 c and BMI in 17 patients were compared.Measurement data with normal distribution were presented as-x ± s and analyzed by the t test.Results All the 17 patients received successful laparoscopic LSG + DJB without conversion to open surgery.The operation time,volume of intraoperative blood loss and recovery time of postoperative gastrointestinal function were (141 ±53)minutes,40 mL and 2.5 days.Of 3 patients with postoperative complications,1 patient with anastomotic leakage at postoperative day 5 received reoperation by laparoscopic Roux-en-Y gastric bypass,1 patient with digestive tract obstruction at postoperative day 10 released obstruction by reoperation and 1 patient with left subphrenic abscess and leakage at the upper of the stomach at postoperative week 2 was cured by the symptomatic treatment.The duration of hospital stay was 5.2 days.All the patients were followed up for a median time of 16 months (range,13-24 months).The postoperative 12-month fasting blood glucose,postprandial 2-hour blood glucose,HbA1c and BMI in 17 patients were (5.5 ± 0.7)mmol/L,(8.8 ± 1.7)mmol/L,5.1％ ± 0.7％ and (24.7 ± 2.3)kg/m2,which were significantly different from preoperative indicators (t =19.96,10.52,12.06,31.99,P ＜ 0.05).During the follow-up,no anastomotic ulcer and stenosis,dumping syndrome and severe malnutrition were occurred.Conclusion LSG + DJB is safe and feasible for the treatment of type 2 diabetes mellitus,with a good short-term hypoglycemic effect.
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Cell therapy has a very promising potential for end-stage liver diseases (ESLD).Fetal liver stem/progenitor cells (FLSPCs) have advantages of safety,high survival and proliferation rates,and a small volume,all which make them ideal for liver disease stem cell therapy.During the early phase of our study,we applied a three-step separation method to enrich FLSPCs and obtained a separation efficiency similar to that of the flow-cell sorting method.Additionally,using a fulminant hepatic failure model in rats,we have demonstrated that FLSPCs can contribute to morphological and functional recovery of the liver.This manuscript will discuss how FLSPCs can be induced to accurately differentiate into hepatocytes and cholangiocytes and how FLSPCs maintain self-renewal.The Notch signaling plays a critical role in regulating the differentiation and self-renewal of many types of stem cells.Our previous findings have shown that the Notch signaling plays an important role in FLSPCs differentiation into hepatocytes.Therefore,the Notch signaling might be involved in the differentiation and self-renewal of FLSPCs.We conducted a study on the regulatory effects and relative molecular mechanisms of the Notch signaling on FLSPCs and found the corresponding interfering target,which might become an index for the clinical application of FLSPCs.
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Objective To study the effect of S-adenomethionine on early stage recovery of transplanted liver.Methods From January 2010 to October 2012,57 liver transplantation patients were divided into 2 groups beginning the first day:group A,23 patients were treated with routine liver-protecting therapy,including glycyrrhizin,glutathione,albumin; group B,34 patients treated with additional S-adenomethionine (Transmetil).AST,ALT,T-BIL,D-BIL,γ-GT,ALB and ALP were compared between the two groups at pre-operation and post-operation day 1,day 4,day 7 and day 14.Results All patients suffered from preoperative hyperbilirubinemia,decreased ALB and elevated concentration of AST,ALT,γ-GT and ALP.On the first day after transplant,AST,ALT,T-BIL,D-BIL and γ-GT elevated and ALB decreased significantly in all cases compared with that before operation (respectively t =10.493,7.089,6.584,15.134,5.164,10.344,5.289,13.034,3.389,4.366,all P ＜ 0.01).On the contrary,the value of ALB was lower (respectively t =8.239,11.662,all P ＜ 0.05).On the fourth day posttransplant,ALB level was higher and that of other parameters were lower in group B when compared with group A (respectively t =2.536,2.736,2.218,3.318,4.804,2.892,all P ＜ O.05).This tendency of liver function improvement continued till postoperative day 7 in all cases while the differences between the two groups remained significant (respectively t =6.107,3.256,2.929,11.688,8.964,2.857,all P ＜ 0.05)except for γ-GT.On day 14,while T-BIL and D-BIL in group B were lower than that in group A (respectively t =4.413,8.493,all P ＜0.001),differences of liver functions were not significant between the two groups (respectively t =1.916,1.414,1.168,1.035,1.604,all P ＞ 0.05).Conclusions Transmetil promotes the recovery of transplanted liver's function,elevates the concentrantion of ALB and reduces the concentration of AST,ALT,T-BIL,D-BIL,γ-GT and ALP at early stage after liver transplant.
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Objective To develop an ideal cultural method to amplify embryonic hepatic stem cells and inhibit their differentiation in vitro. Methods Suspension of ED 14 Fischer (F) 344 rat em-bryonic hepatic stem cells was prepared by collagenase digestion and mechanical disaggregation. Then cells were divided into two groups randomly. The cells in group 1 were seeded into type I collagen-coated plates by adherent culture while those in group 2 were seeded into soft agar medium by suspen-sion culture. After culture for 2 weeks, the morphology and ultrastructure of cells in both groups were observed and compared by inverted microscope and transmission electron microscope, respectivley.The expression of CD90. 1 and CD49F, the two specific stem cell surface markers, was tested by flow cytometry to manifest the establishment of embryonic hepatic stem cells. Alkaline phosphatase stai-ning was used to detect stem cell differentiation. Result Embryonic hepatic stem cells in group 2 were characterized by higher nucleus-cytoplasm ratio and less cell organelles, higher expression of CD90. 1 and CD49F, and stronger positive reaction for alkaline phosphatase staining compared with those in group 1. Moreover, the cells in group 1 showed significant differentiation features. Conclusion Em-bryonic hepatic stem cells cultured suspendedly in soft agar medium experience less differentiation than those adherently cultured in serum-added culture medium, and can proliferate and form clone ball with a specific stem cell feature.
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Auxiliary liver transplantation reserves whole or part of recipient' native liver while implanting the graft. It call be classified as auxiliary heterotopic liver transplantation and auxiliary orthotopic liver transplantation according to the location of the graft. On the basis of graft volume. it can be categorized as whole liver auxiliary liver transplantation and partial liver auxiliary liver transplantation. Either cadaveric or living donor is available. Because auxiliarg orthotopic liver transplantation is only the partial liver transplantation, so it is also called aunliry orthotopic partial liver transplantation. The. technique of auxiliary liver transplantation progresses with the devehopment of liver transplantation. Great attention is paid to auxiliary liver transplantation because of its special superiority, in spite of some unresolved problems.