1.Role of the portal system in liver regeneration:From molecular mechanisms to clinical management
Xu HANZHI ; Qiu XUN ; Wang ZHOUCHENG ; Wang KAI ; Tan YAWEN ; Gao FENGQIANG ; Perini Vinicius MARCOS ; Xu XIAO
Liver Research 2024;8(1):1-10
The liver has a strong regenerative capacity that ensures patient recovery after hepatectomy and liver transplantation.The portal system plays a crucial role in the dual blood supply to the liver,making it a significant factor in hepatic function.Several surgical strategies,such as portal vein ligation,associating liver partition and portal vein ligation for staged hepatectomy,and dual vein embolization,have high-lighted the portal system's importance in liver regeneration.Following hepatectomy or liver trans-plantation,the hemodynamic properties of the portal system change dramatically,triggering regeneration via shear stress and the induction of hypoxia.However,excessive portal hyperperfusion can harm the liver and negatively affect patient outcomes.Furthermore,as the importance of the gut-liver axis has gradually been revealed,the effect of metabolites and cytokines from gut microbes carried by portal blood on liver regeneration has been acknowledged.From these perspectives,this review outlines the molecular mechanisms of the portal system's role in liver regeneration and summarizes therapeutic strategies based on the portal system intervention to promote liver regeneration.
2.Evaluating clinical significance of ductular reaction in liver transplantation
Xinhao HU ; Tianchen LAN ; Jian CHEN ; Zhetuo QI ; Fengqiang GAO ; Hao CHEN ; Libin DONG ; Xinyu YANG ; Shusen ZHENG ; Xiao XU
Chinese Journal of Organ Transplantation 2024;45(8):550-557
Objective:To explore the role of ductular reaction in assessing the efficacy of liver transplantation.Method:From January 2015 to December 2020, he relevant clinical data were retrospectively reviewed for 100 recipients and their corresponding donors at Shulan (Hangzhou) Hospital. They were assigned into two groups of hepatic steatosis (HS group, 65 cases) and non-hepatic steatosis (non-HS group, 35 cases) according to whether or not receiving steatosis donated liver. Furthermore, based upon the occurrence of early allograft dysfunction (EAD), the participants were categorized into two groups of EAD (33 cases) and non-EAD (67 cases). The degree of bile duct reaction ductular reaction was defined by the percentage of staining area occupied by cytokeratin 19 (CK19) -positive bile duct cells in immunohistochemical-stained specimens. Donor of ductular reaction were compared between HS/non-HS and EAD/non-EAD groups. The risk factors for EAD were identified by univariate and multivariate Logistic regression analysis. Subgroup analysis was conducted based upon the level of ductular reaction (DR number) in donors (DR=0.4 as a threshold) and whether or not donors exhibited steatosis. The impact of DR was examined on the incidence of EAD and survival post-liver transplantation in steatosis donors.Result:The level of DR was higher in steatosis donor than that in non-steatosis donor [ (0.59%±0.385%) vs. (0.32%±0.194%), P<0.01]. And it was higher in EAD group than that in non-EAD group [ (0.72%±0.449%) vs. (0.38%±0.226%), P<0.01]. Multivariate logistic regression analysis showed that a high level of ductular reaction was an independent risk factor for EAD post-liver transplantation in donor. Subgroup analysis revealed that receiving a steatosis donor with low ductular reaction (DR<0.4%) had comparable levels of EAD occurrence and overall survival rate to receiving a non-steatosis donor. Conclusion:Steatosis with low ductular reaction donor may be safely applied for liver transplantation. And assessing donor injury based upon ductular reaction can effectively expand the clinical application of steatosis donors.
3.Morphological observation of bovine kidney (MDBK) cells effected by foot-and-mouth disease virus L(pro).
Fengqiang HAO ; Guozheng CONG ; Shandian GAO ; Tong LIN ; Junzheng DU ; Junjun SHAO ; Huiyun CHANG
Chinese Journal of Biotechnology 2009;25(11):1614-1620
In order to explore the morphological changes of Bovine Kidney (MDBK) cells induced by foot-and-mouth disease virus (FMDV) L protease, we induced the expression of FMDV L protease in bovine kidney cells (MDBK) artificially. All work is carried out on the basis of a stable MDBK cell line inducibly expresses the Lab gene under the control of tetracycline. We use cell morphology, Hoechst 33258 staining, AO-EB staining, and DNA Ladder abstraction to research the morphological changes of MDBK cells. 24 hours after FMDV L protease were induced and expressed in MDBK cells, cells shown the diminish of cell size, nuclear enrichment and the appearance of transparency circle under the light microscope. Apoptosis characteristics of nuclear condensation, fragmentation, accompanied by apoptotic bodies formation (Hoechst 33258 staining). 36 hours after the expression, nuclear staining of early lesions showed bright green plaque or debris-like dense, and advanced lesions showed Orange and dense plaques (AO-EB staining). 48 hours after the expression, DNA gel electrophoresis showed visible DNA ladder. Results indicate that FMDV L protease can induce apoptosis of MDBK and apoptosis plays an important role in the cytopathogenicity effect of FMDV.
Animals
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Cattle
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Cell Line
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Endopeptidases
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biosynthesis
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genetics
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Foot-and-Mouth Disease Virus
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pathogenicity
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Kidney
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cytology
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pathology
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virology
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Transfection
4.The clinical practice and consideration for donor liver expansion
Kai WANG ; Fengqiang GAO ; Xiao XU
Chinese Journal of Surgery 2023;61(10):826-832
Liver transplantation is the most effective method to address end-stage liver disease. However, there is a huge imbalance between organ supply and demand in China. Recently,effective expansion of the donor liver has become a hot research direction in academia. Authors′ group comprehensively integrates domestic and foreign evidence-based medical evidence, the latest academic outcomes and clinical experience. Based on the innovative viewshed of crossfusion between biomedical engineering and medicine, author group systematically elaborate in the main strategies for expanding the liver donor pool, including the multichannel expansion of marginal donor liver,multidimensional innovation of technologies in transplant surgery and diversified exploration of alternative resources of organs. The author group aims to promote the construction of a large cohort,the integration of big data,and the output of high quality research,achieving innovative theory and clinical translation in organ transplantation,thus promoting the higher quality development of liver transplantation in China.
5.The clinical practice and consideration for donor liver expansion
Kai WANG ; Fengqiang GAO ; Xiao XU
Chinese Journal of Surgery 2023;61(10):826-832
Liver transplantation is the most effective method to address end-stage liver disease. However, there is a huge imbalance between organ supply and demand in China. Recently,effective expansion of the donor liver has become a hot research direction in academia. Authors′ group comprehensively integrates domestic and foreign evidence-based medical evidence, the latest academic outcomes and clinical experience. Based on the innovative viewshed of crossfusion between biomedical engineering and medicine, author group systematically elaborate in the main strategies for expanding the liver donor pool, including the multichannel expansion of marginal donor liver,multidimensional innovation of technologies in transplant surgery and diversified exploration of alternative resources of organs. The author group aims to promote the construction of a large cohort,the integration of big data,and the output of high quality research,achieving innovative theory and clinical translation in organ transplantation,thus promoting the higher quality development of liver transplantation in China.
6.Prognostic analysis of steatosis donor liver transplantation: a multicenter clinical trial
Fengqiang GAO ; Kai WANG ; Libin DONG ; Zhisheng ZHOU ; Xuyong WEI ; Li ZHUANG ; Wan LI ; Guoyue LYU ; Shusen ZHENG ; Xiao XU
Chinese Journal of Organ Transplantation 2023;44(1):23-30
Objective:To explore the early and medium-long term outcomes of steatosis donor liver transplantation(LT)for an optimal clinical application.Methods:From January 2015 to December 2020, this retrospective cohort study was conducted jointly at Shulan (Hangzhou) Hospital, First Affiliated Hospital of Zhejiang University and First Hospital of Jilin University. The relevant clinicopathological and follow-up data were collected from 1535 LT recipients. For comparison, propensity score was utilized for case-control matching of steatosis and non-steatosis donor livers. According to presence or absence of liver steatosis, the recipients were divided into two groups of steatosis donor liver (n=243) and non-steatosis donor liver (n=1292). And 1∶1 propensity score matching was made for two groups. Then early and medium-long term outcomes of two groups were examined. Counts were described as absolute numbers. Kaplan-Meier method was employed for calculating survival time and plotting survival curve and Log-rank test for survival analysis. COX regression model was utilized for univariate and multivariate analyses. Based on basic metabolic disease pre-LT, steatosis donor liver recipients were divided into three subgroups: BMI ≥25 kg/m 2 with hypertension or diabetes (n=21), BMI<25 kg/m 2 and no hypertension or diabetes (n=130) and other recipients (n=92). A comparative study was performed for determining the prognosis of subgroups according to the different characteristics of recipient and donor liver. Results:No significant inter-group difference existed in 2-year survival post-LT ( P=0.174). However, significant inter-group difference in survival existed after 2 years post-LT ( P=0.004). And 3/5-year survival rate of steatosis donor liver was 66.4% and 44.2% respectively. Both were significantly lower than those of non-steatosis donor liver. Multivariate Cox regression analysis indicated that steatosis donor liver and male recipients were independent risk factors for prognosis >2 years survival post-LT( P=0.008, P=0.004). Subgroup analysis of steatosis liver donors showed that the prognosis of patients with BMI ≥25 kg/m 2 with hypertension or diabetes was significantly worse than other subgroups (BMI <25 kg/m 2 with no hypertension or diabetes and other recipients) <2 years survival post-LT ( P=0.029, P=0.043). Conclusions:Steatosis donor liver does not affect early survival of recipients, yet reduces medium-long term survival rate of recipients notably. In steatosis donor liver recipients, early survival rate declines markedly in recipients with preoperative BMI ≥25 kg/m 2 with hypertension or diabetes as compared with BMI <25 kg/m 2 with no hypertension or diabetes group.