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Pulsed eddy current (PEC) technology serves as a popular testing method for multilayer structures and is widely used in coating and substrate thickness measurement. However, in the coating thickness measurement of a multilayer structure, the substrate thickness effect is a disturbance that needs to be eliminated urgently. In order to reduce the substrate thickness effect, in this paper a twice difference normalisation method is proposed to obtain a signal feature independently of the substrate thickness effect for measuring the coating thickness of a multilayer ferromagnetic structure. The simulation and experimental results demonstrate that a fitting line of the peak value of twice difference normalisation signals can be obtained by using the twice difference normalisation method when only the coating thickness changes. The normalisation fitting line is immune to the substrate thickness effect and can be used to measure the coating thickness of a multilayer ferromagnetic structure, which means that the twice difference normalisation method is feasible for high-precision evaluation of the coating thickness of a multilayer ferromagnetic structure when the substrate thickness changes. This study will improve the coating thickness measurement accuracy of multilayer ferromagnetic structures when the substrate thickness changes in the PEC testing.

Background Macrophages are the major components of tumour microenvironment, which play critical roles in tumour development. Long noncoding RNAs (lncRNAs) also contribute to tumour progression. However, the potential roles of lncRNAs in modulating the interaction between cancer cells and macrophages in hepatocellular carcinoma (HCC) are poorly understood. Methods The expression of lncRNA ZNNT1 in tissues and cells was measured using qRT-PCR. The roles of ZNNT1 in HCC cells and macrophages were investigated using in vitro and in vivo assays. The molecular mechanisms of ZNNT1 were explored using qRT-PCR, RNA immunoprecipitation, RNA pull-down, chromatin immunoprecipitation, enzyme linked immunosorbent assay, and dual-luciferase reporter assays. Results ZNNT1 was identified as an HCC-related lncRNA, which was upregulated and associated with poor prognosis of HCC. ZNNT1 promoted HCC cellular growth, migration, and invasion, and suppressed apoptosis in vitro. ZNNT1 promoted HCC xenograft growth in vivo. Furthermore, ZNNT1 recruited and induced M2 polarization of macrophages. Mechanistically, ZNNT1 upregulated SPP1 expression and osteopontin (OPN) secretion via sponging miR-181a/b/c/d-5p and miR-33a/b-5p. Functional rescue assays identified OPN as the mediator of the oncogenic roles of ZNNT1 in HCC cells and also the effects of ZNNT1 on macrophages. M2 Macrophages-recruited by ZNNT1 enhanced malignant phenotypes of HCC cells, which was mediated by S100A9 secreted by M2 macrophages. Intriguing, S100A9 secreted by M2 macrophages also upregulated ZNNT1 expression in HCC cells via AGER/NF-κB signaling. Conclusions ZNNT1, OPN, and S100A9 formed a positive feedback loop, which promoted macrophages recruitment and M2 polarization, and enhanced malignant features of HCC cells. The ZNNT1/OPN/S100A9 feedback loop represents potential therapeutic target for HCC.

It has been shown that normothermic machine perfusion (NMP), a novel preservation method, is able to assess and resuscitate liver grafts with risk factors. However, there is no consistent criteria for the assessment of liver grafts with NMP. Ischemia-free liver transplantation (IFLT) includes innovative surgical techniques and NMP, which can protect liver grafts from ischemia throughout organ procurement, preservation, and implantation. In our center, 28 human livers from donation after brain death donors were subjected to IFLT between July 2017 and October 2018. The correlation between posttransplant liver function tests with the perfusion parameters, blood gas analysis of perfusate, and bile biochemistry were analyzed. During the preservation phase, the vascular flow was stable, and the lactate level decreased rapidly. The transaminase release in the perfusate was low but stable, whereas the glucose level remained high. The perfusate lactate and aspartate aminotransferase (AST) levels at 1 hour of perfusion were correlated with the posttransplant peak AST level. There were negative correlations between the portal vein and hepatic artery flows at the end of perfusion and the peak transaminase levels within 7 days after transplantation. In conclusion, during IFLT, NMP is able to bridge the liver grafts from donors to recipients and can allow the assessment of liver function by perfusion characteristics.

Background As a critical metabolic substrate, glutamine is not only involved in the progression of many cancers but is also related to angiogenesis. Glutamate dehydrogenase (GLDH), a key enzyme in glutamine metabolism, has been reported to regulate tumor proliferation; however, its relationship with microvascular invasion (MVI) is unclear. This study evaluated the ability of preoperative serum GLDH levels to predict MVI and the long-term survival of hepatocellular carcinoma (HCC) patients after liver transplantation (LT). Methods HCC patients that underwent LT from January 2015 to May 2020 at the First Affiliated Hospital of Sun Yat-Sen University were enrolled in our retrospective analysis. Clinicopathological variables were extracted from medical records. A receiver operating characteristic curve was created to determine the optimal cut-off value of GLDH for MVI. Results Preoperative GLDH was significantly elevated in the MVI-positive group (U = 454.00, p = 0.000). The optimal cut-off value of GLDH for MVI was 7.45 U/L, with an area under the curve of 0.747 (95% CI [0.639–0.856], p = 0.000). The sensitivity was 79.3%, while the specificity was 64.5%. GLDH > 7.45 U/L (p = 0.023) and maximum diameter >5 cm (p = 0.001) were independent risk factors for the presence of MVI. Patients with GLDH > 7.45 U/L had significantly poorer overall survival (p = 0.001) and recurrence-free survival (p = 0.001) after LT than patients with GLDH ≤ 7.45 U/L. Similarly, patients with MVI were associated with poor survival (p = 0.000). Conclusions Preoperative elevated serum GLDH levels predict MVI and poorer long-term survival for HCC after LT.

Background Radiomics can improve the accuracy of traditional image diagnosis to evaluate extrahepatic cholangiocarcinoma (ECC); however, this is limited by variations across radiologists, subjective evaluation, and restricted data. A radiomics-based particle swarm optimization and support vector machine (PSO-SVM) model may provide a more accurate auxiliary diagnosis for assessing differentiation degree (DD) and lymph node metastasis (LNM) of ECC. Objective The objective of our study is to develop a PSO-SVM radiomics model for predicting DD and LNM of ECC. Methods For this retrospective study, the magnetic resonance imaging (MRI) data of 110 patients with ECC who were diagnosed from January 2011 to October 2019 were used to construct a radiomics prediction model. Radiomics features were extracted from T1-precontrast weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) using MaZda software (version 4.6; Institute of Electronics, Technical University of Lodz). We performed dimension reduction to obtain 30 optimal features of each sequence, respectively. A PSO-SVM radiomics model was developed to predict DD and LNM of ECC by incorporating radiomics features and apparent diffusion coefficient (ADC) values. We randomly divided the 110 cases into a training group (88/110, 80%) and a testing group (22/110, 20%). The performance of the model was evaluated by analyzing the area under the receiver operating characteristic curve (AUC). Results A radiomics model based on PSO-SVM was developed by using 110 patients with ECC. This model produced average AUCs of 0.8905 and 0.8461, respectively, for DD in the training and testing groups of patients with ECC. The average AUCs of the LNM in the training and testing groups of patients with ECC were 0.9036 and 0.8889, respectively. For the 110 patients, this model has high predictive performance. The average accuracy values of the training group and testing group for DD of ECC were 82.6% and 80.9%, respectively; the average accuracy values of the training group and testing group for LNM of ECC were 83.6% and 81.2%, respectively. Conclusions The MRI-based PSO-SVM radiomics model might be useful for auxiliary clinical diagnosis and decision-making, which has a good potential for clinical application for DD and LNM of ECC.

Currently, ex situ machine perfusion is a burgeoning technique that provides a better preservation method for donor organs than conventional static cold preservation (0-4 °C). A continuous blood supply to organs using machine perfusion from procurement and preservation to implantation facilitates complete prevention of ischemia reperfusion injury and permits ex situ functional assessment of donor livers before transplantation. In this manuscript, we provide a step-by-step ischemia-free liver transplantation protocol in which an ex situ normothermic machine perfusion apparatus is used for pulsatile perfusion through the hepatic artery and continuous perfusion of the portal vein from human donor livers to recipients. In the perfusion period, biochemical analysis of the perfusate is conducted to assess the metabolic activity of the liver, and a liver biopsy is also performed to evaluate the degree of injury. Ischemia-free liver transplantation is a promising method to avoid ischemia-reperfusion injury and may potentially increase the donor pool for transplantation.

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BACKGROUND Radiomics can improve the accuracy of traditional image diagnosis to evaluate extrahepatic cholangiocarcinoma (ECC); however, this is limited by variations across radiologists, subjective evaluation, and restricted data. A radiomics-based particle swarm optimization and support vector machine (PSO-SVM) model may provide a more accurate auxiliary diagnosis for assessing differentiation degree (DD) and lymph node metastasis (LNM) of ECC. OBJECTIVE The objective of our study is to develop a PSO-SVM radiomics model for predicting DD and LNM of ECC. METHODS For this retrospective study, the magnetic resonance imaging (MRI) data of 110 patients with ECC who were diagnosed from January 2011 to October 2019 were used to construct a radiomics prediction model. Radiomics features were extracted from T1-precontrast weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) using MaZda software (version 4.6; Institute of Electronics, Technical University of Lodz). We performed dimension reduction to obtain 30 optimal features of each sequence, respectively. A PSO-SVM radiomics model was developed to predict DD and LNM of ECC by incorporating radiomics features and apparent diffusion coefficient (ADC) values. We randomly divided the 110 cases into a training group (88/110, 80%) and a testing group (22/110, 20%). The performance of the model was evaluated by analyzing the area under the receiver operating characteristic curve (AUC). RESULTS A radiomics model based on PSO-SVM was developed by using 110 patients with ECC. This model produced average AUCs of 0.8905 and 0.8461, respectively, for DD in the training and testing groups of patients with ECC. The average AUCs of the LNM in the training and testing groups of patients with ECC were 0.9036 and 0.8889, respectively. For the 110 patients, this model has high predictive performance. The average accuracy values of the training group and testing group for DD of ECC were 82.6% and 80.9%, respectively; the average accuracy values of the training group and testing group for LNM of ECC were 83.6% and 81.2%, respectively. CONCLUSIONS The MRI-based PSO-SVM radiomics model might be useful for auxiliary clinical diagnosis and decision-making, which has a good potential for clinical application for DD and LNM of ECC.

Background Solitary fibrous tumor (SFT) is a rare soft tissue tumor originating from mesenchyme. Two cases of SFT we report right now occurred in the splenic vein and liver respectively, this primary splenic vein SFT may be the first report case, and also the first report of liver recurrence SFT cured by orthotopic liver transplantation (OLT). Case presentation One case was a 37-year-old female patient whose primary tumor site was located in the splenic vein, which resulted in splenomegaly and hypersplenism; its recurrence again and again after surgical resection and eventually transferred to the liver, during 10 years of follow-up, 4 operations were performed, and he is in a good condition right now. The second case was a 54-year-old male patient whose primary tumor site was located in the liver, spleen and left side of the chest wall; however, he had no uncomfortable symptoms. Surgeons performed two operations to remove these tumors, totally. 6 years later, SFT recurrence in the liver, and given that the tumor was so large that it could not be completely surgical resected, we chose orthotopic liver transplantation (OLT), and no tumor recurrence during 12-month follow-up. Conclusion The reports of these two cases of SFT are very rare, especially the splenic vein SFT, which expand the understanding of SFT. The main treatment of SFT is still surgical resection, right now, and liver transplantation may be a new option treatment for the huge liver SFT.

BACKGROUNDIschemia-reperfusion injury is considered an inevitable event that compromises posttransplant outcomes. Numerous treatments have been proposed to reduce its impact. However, most of them have had limited success, as none of them can completely avoid graft ischemia.METHODSIschemia-free liver transplantation (IFLT) comprises surgical techniques to enable continuous oxygenated blood supply to brain-dead donor livers during procurement, preservation and implantation using normothermic machine perfusion technology. In this nonrandomized study, 38 donor livers were transplanted using IFLT and were compared to 130 livers procured and transplanted using a conventional procedure (CLT).RESULTSOne patient (2.6%) suffered early allograft dysfunction in the IFLT group, compared with 43.8% of patients in the CLT group (absolute risk difference, 41.2 percentage points; 95% confidence interval, −31.3, −51.1). The median (range) peak aspartate aminotransferase levels within the first week (336, 149-4112 vs. 1445, 149-25083 U/L, PCONCLUSIONSIFLT provides a new approach to minimize ischemia-reperfusion injury and improve post-transplant outcomes.Clinical trial registryThis trial is registered with http://www.chictr.org.cn, number ChiCTR-OPN-17012090.

Carbon monoxide (CO) poisoning, the most frequent type of poisoning, alters hemodynamics and creates tissue hypoxia that ultimately leads to thromboembolism. We herein describe a previously healthy 17-year-old male patient who developed acute CO poisoning while bathing in the same room as a gas heater. He was first treated with urokinase thrombolytic therapy at a local hospital, which proved ineffective. The patient was admitted to our hospital with unstable circulation and was diagnosed with massive pulmonary embolism combined with multiple organ dysfunction syndrome. His Acute Physiology and Chronic Health Evaluation II score was 22, and his Sequential Organ Failure Assessment score was 15. We faced a difficult decision regarding whether to perform surgical embolectomy or to repeat the thrombolysis. We opted to repeat the thrombolysis with successful results. Our experience may help clinicians manage similar cases in the future.

Fibroblast growth factor (FGF) has been considered to modulate liver regeneration (LR) after partial hepatectomy (PH) at the tissue level. Previous studies have demonstrated that FGF15 and FGF19 induce the activation of its receptor, FGF receptor 4 (FGFR4), which can promote hepatocellular carcinoma progression and regulate liver lipid metabolism. In this study, we aimed to explore the role of the ileal FGF15/19- hepatic FGFR4 axis in the LR after PH. Male C57BL/6 mice aged 8-12 weeks were partially hepatectomized and assessed for expression of ileal FGF15/19 to hepatic FGFR4 signaling. We used recombinant human FGF19 protein and a small interfering RNA (siRNA) of FGFR4 to regulate expression of the FGF15/19-FGFR4 axis in vitro and in vivo. The proliferation and cell cycle of hepatocytes, the expression levels of FGF15/19-FGFR4 downstream molecules, liver recovery, and lipid metabolism were assessed. We found that both ileal and serum FGF15 expression were upregulated and hepatic FGFR4 was activated after PH in mice. FGF15/19 promoted cell cycle progression, enhanced proliferation, and reduced hepatic lipid accumulation of hepatocytes both in vitro and in vivo. Furthermore, the proliferative effect and lipid regulatory properties of FGF15/19 were dependent on FGFR4 in hepatocytes. In addition, ileal FGF15/19-hepatic FGFR4 transduction during hepatocyte proliferation was regulated by extracellular regulated protein kinase (ERK) 1/2. In conclusion, the ileal FGF15/19 to hepatic FGFR4 axis is activated and promotes LR after PH in mice, supporting the potential of ileal FGF15/19 to hepatic FGFR4 axis-targeted therapy to enhance LR after PH.

Summary Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences. Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT). Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p

Background Natural language processing (NLP) is an important traditional field in computer science, but its application in medical research has faced many challenges. With the extensive digitalization of medical information globally and increasing importance of understanding and mining big data in the medical field, NLP is becoming more crucial. Objective The goal of the research was to perform a systematic review on the use of NLP in medical research with the aim of understanding the global progress on NLP research outcomes, content, methods, and study groups involved. Methods A systematic review was conducted using the PubMed database as a search platform. All published studies on the application of NLP in medicine (except biomedicine) during the 20 years between 1999 and 2018 were retrieved. The data obtained from these published studies were cleaned and structured. Excel (Microsoft Corp) and VOSviewer (Nees Jan van Eck and Ludo Waltman) were used to perform bibliometric analysis of publication trends, author orders, countries, institutions, collaboration relationships, research hot spots, diseases studied, and research methods. Results A total of 3498 articles were obtained during initial screening, and 2336 articles were found to meet the study criteria after manual screening. The number of publications increased every year, with a significant growth after 2012 (number of publications ranged from 148 to a maximum of 302 annually). The United States has occupied the leading position since the inception of the field, with the largest number of articles published. The United States contributed to 63.01% (1472/2336) of all publications, followed by France (5.44%, 127/2336) and the United Kingdom (3.51%, 82/2336). The author with the largest number of articles published was Hongfang Liu (70), while Stéphane Meystre (17) and Hua Xu (33) published the largest number of articles as the first and corresponding authors. Among the first author’s affiliation institution, Columbia University published the largest number of articles, accounting for 4.54% (106/2336) of the total. Specifically, approximately one-fifth (17.68%, 413/2336) of the articles involved research on specific diseases, and the subject areas primarily focused on mental illness (16.46%, 68/413), breast cancer (5.81%, 24/413), and pneumonia (4.12%, 17/413). Conclusions NLP is in a period of robust development in the medical field, with an average of approximately 100 publications annually. Electronic medical records were the most used research materials, but social media such as Twitter have become important research materials since 2015. Cancer (24.94%, 103/413) was the most common subject area in NLP-assisted medical research on diseases, with breast cancers (23.30%, 24/103) and lung cancers (14.56%, 15/103) accounting for the highest proportions of studies. Columbia University and the talents trained therein were the most active and prolific research forces on NLP in the medical field.

BACKGROUND Natural language processing (NLP) is an important traditional field in computer science, but its application in medical research has faced many challenges. With the extensive digitalization of medical information globally and increasing importance of understanding and mining big data in the medical field, NLP is becoming more crucial. OBJECTIVE The goal of the research was to perform a systematic review on the use of NLP in medical research with the aim of understanding the global progress on NLP research outcomes, content, methods, and study groups involved. METHODS A systematic review was conducted using the PubMed database as a search platform. All published studies on the application of NLP in medicine (except biomedicine) during the 20 years between 1999 and 2018 were retrieved. The data obtained from these published studies were cleaned and structured. Excel (Microsoft Corp) and VOSviewer (Nees Jan van Eck and Ludo Waltman) were used to perform bibliometric analysis of publication trends, author orders, countries, institutions, collaboration relationships, research hot spots, diseases studied, and research methods. RESULTS A total of 3498 articles were obtained during initial screening, and 2336 articles were found to meet the study criteria after manual screening. The number of publications increased every year, with a significant growth after 2012 (number of publications ranged from 148 to a maximum of 302 annually). The United States has occupied the leading position since the inception of the field, with the largest number of articles published. The United States contributed to 63.01% (1472/2336) of all publications, followed by France (5.44%, 127/2336) and the United Kingdom (3.51%, 82/2336). The author with the largest number of articles published was Hongfang Liu (70), while Stéphane Meystre (17) and Hua Xu (33) published the largest number of articles as the first and corresponding authors. Among the first author’s affiliation institution, Columbia University published the largest number of articles, accounting for 4.54% (106/2336) of the total. Specifically, approximately one-fifth (17.68%, 413/2336) of the articles involved research on specific diseases, and the subject areas primarily focused on mental illness (16.46%, 68/413), breast cancer (5.81%, 24/413), and pneumonia (4.12%, 17/413). CONCLUSIONS NLP is in a period of robust development in the medical field, with an average of approximately 100 publications annually. Electronic medical records were the most used research materials, but social media such as Twitter have become important research materials since 2015. Cancer (24.94%, 103/413) was the most common subject area in NLP-assisted medical research on diseases, with breast cancers (23.30%, 24/103) and lung cancers (14.56%, 15/103) accounting for the highest proportions of studies. Columbia University and the talents trained therein were the most active and prolific research forces on NLP in the medical field.

Background Radiomics can improve the accuracy of traditional image diagnosis to evaluate extrahepatic cholangiocarcinoma (ECC); however, this is limited by variations across radiologists, subjective evaluation, and restricted data. A radiomics-based particle swarm optimization and support vector machine (PSO-SVM) model may provide a more accurate auxiliary diagnosis for assessing differentiation degree (DD) and lymph node metastasis (LNM) of ECC. Objective The objective of our study is to develop a PSO-SVM radiomics model for predicting DD and LNM of ECC. Methods For this retrospective study, the magnetic resonance imaging (MRI) data of 110 patients with ECC who were diagnosed from January 2011 to October 2019 were used to construct a radiomics prediction model. Radiomics features were extracted from T1-precontrast weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) using MaZda software (version 4.6; Institute of Electronics, Technical University of Lodz). We performed dimension reduction to obtain 30 optimal features of each sequence, respectively. A PSO-SVM radiomics model was developed to predict DD and LNM of ECC by incorporating radiomics features and apparent diffusion coefficient (ADC) values. We randomly divided the 110 cases into a training group (88/110, 80%) and a testing group (22/110, 20%). The performance of the model was evaluated by analyzing the area under the receiver operating characteristic curve (AUC). Results A radiomics model based on PSO-SVM was developed by using 110 patients with ECC. This model produced average AUCs of 0.8905 and 0.8461, respectively, for DD in the training and testing groups of patients with ECC. The average AUCs of the LNM in the training and testing groups of patients with ECC were 0.9036 and 0.8889, respectively. For the 110 patients, this model has high predictive performance. The average accuracy values of the training group and testing group for DD of ECC were 82.6% and 80.9%, respectively; the average accuracy values of the training group and testing group for LNM of ECC were 83.6% and 81.2%, respectively. Conclusions The MRI-based PSO-SVM radiomics model might be useful for auxiliary clinical diagnosis and decision-making, which has a good potential for clinical application for DD and LNM of ECC.

IntroductionDuring conventional liver transplantation (CLT), ischaemia-reperfusion injury (IRI) is inevitable and is associated with complications such as early allograft dysfunction (EAD), primary non-function and ischaemic-type biliary lesions. We have established a novel procedure called ischaemia-free liver transplantation (IFLT). The results from a pilot study suggest that IFLT might prevent IRI and yield better transplant outcomes than CLT. The purpose of this study was to further assess the efficacy and safety of IFLT versus CLT in patients with end-stage liver disease.Methods and analysisThis is an investigator-initiated, open-label, phase III, prospective, single-centre randomised controlled trial on the effects of IFLT in patients with end-stage liver disease. Adult patients (aged 18–75 years) eligible for liver transplantation will be screened for participation in this trial and will be randomised between the IFLT group (n=34) and the CLT group (n=34). In the IFLT group, the donor liver will be procured, preserved and implanted with continuous normothermic machine perfusion (NMP). In the CLT group, the donor liver will be procured after a fast cold flush, preserved in 0°C–4°C solution and implanted under hypothermic and hypoxic conditions. Patients in both groups will be managed according to the standard protocol of our centre. The primary end point is the incidence of EAD after liver transplantation. Intraoperative and postoperative parameters of donor livers and recipients will be observed and recorded, and postoperative liver graft function, complications and recipient and graft survival will be evaluated. After a 12-month follow-up of the last enrolled recipient, the outcomes will be analysed to evaluate the safety and efficacy of IFLT versus CLT in patients with end-stage liver disease.Ethics and disseminationThe protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Sun Yat-sen University. The findings will be disseminated to the public through conference presentations and peer-reviewed scientific journals.Trial registration numberChiCTR1900021158.

BACKGROUND In contrast to conventional static cold preservation, normothermic machine perfusion (NMP) provides a beneficial alternative preservation of donor livers. However, the liver still suffered cold ischemic injury before attaching to the perfusion device. MATERIAL AND METHODS To prevent cold ischemic injury during procurement, we describe a novel procedure called ischemia-free liver procurement (IFLP) under NMP. Two liver grafts were procured from brain death donor under NMP and underwent 2-hour ex vivo NMP followed by 3 and 6 hours of static cold preservation. From procurement to post-transplantation course, evidence was collected to prove that IFLP is safe and benefits recipients. RESULTS The post-transplantation course was uneventful, and the liver function tests and histological study revealed minimal hepatocyte and biliary epithelium injury during the preservation. CONCLUSIONS This preliminary experience demonstrates the clinical feasibility and safety of IFLP under NMP which offering opportunities to increase the number of donor livers and to improve the organ function.

Background This study aimed to investigate the tolerogenic mechanisms induced by semimature dendritic cells (smDCs) and regulatory dendritic cells (regDCs) after transplantation of hepatocytes differentiated from mouse embryonic stem cells (ESCs) and to confirm the low immunogenicity of hepatocytes differentiated from ESCs. Methods Green fluorescent protein-labeled ESCs collected from 129 mice were cultured to differentiate into hepatocytes. smDCs and regDCs were cultured in vitro. The hepatocytes were cultured after being extracted from the livers of 129 mice. After injecting smDCs or regDCs 3 days in advance, these differentiated hepatocytes and normal hepatocytes were transplanted into the livers of BALB/c mice separately. Subsequently, the histopathological features and cytokines in transplant tissues as well as the Foxp3 expression in peripheral blood CD4+ T cells of the recipients were examined. Results The morphological phenotypes of smDCs and regDCs were similar. They both expressed medium levels of MHC-II, CD40, CD80, and CD86, high levels of TGF-β and IL-10, and low levels of IL-2. The survival of differentiated hepatocytes was prolonged and inflammatory infiltration in transplant tissues was reduced in both the smDC and regDC groups. Foxp3 expression in peripheral blood CD4+ T cells of the smDC group increased to 5.38% and that of the regDC group also rose to 3.87%. Moreover, the inflammatory infiltration in the tissues receiving transplanted hepatocytes was more obvious. Conclusions smDCs and regDCs were similar tolerogenic dendritic cells. They both could alleviate the immune injury by inducing CD4+CD25+Foxp3+ regulatory T cells through the medium expression of MHC-II, CD40, CD80, and CD86 and the appropriate secretion of cytokines. Hepatocytes differentiated from ESCs displayed low immunogenicity.

Summary Background Paediatric liver allografts sometimes are allocated to adult recipients when there are no suitable paediatric recipients on the waiting list. However, debate exits regarding the reported outcomes of liver transplants using such small grafts. Methods Records from adult patients undergoing liver transplantation between February 2010 and January 2016 who received whole grafts from paediatric (≤ 13 years) donors or ideal deceased adult (18–35 years) donors were reviewed. Patient and graft survival, post-transplant liver function, and complications between the two groups were compared. Results The baseline characteristics were comparable, except that the paediatric donor allografts had smaller size. The 3-month, 1-year, and 3-year rates of patient survival were 91.3%, 85.2%, and 85.2% in the paediatric donor group and 93.4%, 88.9%, and 85.0% in the adult donor group (P = 0.947), respectively. One patient receiving a paediatric allograft developed small-for-size liver syndrome post-transplantation. There was no difference in primary non-function, early allograft dysfunction, biliary complications, vascular complications, or infection between the two groups. Conclusion Our study indicates that using paediatric donor livers in well-selected adult recipients is a safe procedure, considering there was no suitable paediatric recipient. However, the risk of portal hyperperfusion should be considered in clinical cases such as size-mismatched transplants.

Summary Background The immunosuppression of tumor-infiltrating lymphocytes (TILs) is associated with rapid progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). T cell Ig- and mucin-domain-containing molecule-3 (Tim-3) and programmed cell death 1 (PD-1) are important inhibitory molecules expressed on the surface of T cells, but their roles in the function of TILs in HBV-HCC are poorly understood. We aimed to study the roles of these two markers in HBV-HCC. Methods Ninety patients with pathologically confirmed HBV-associated HCC were enrolled in our study. Blood samples, paired fresh tumor tissues and adjacent tissues were collected, and isolating peripheral blood mononuclear cells, TILs and adjacent-infiltrating lymphocytes were isolated from these samples. The patients were followed-up to allow survival analysis. Results Tim-3 or/and PD-1 was up-regulated expressed on CD4+ and CD8+ TILs in HBV-HCC patients and a higher proportion of TILs expressed PD-1 alone. Tim-3+ and PD-1+ TILs greatly decreased secretion of IFN-? and TNF-a. Expression of Tim-3 and PD-1 on TILs negatively correlated with disease-free survival of HCC patients. Direct blockade of Tim-3 and PD-1 in vitro significantly enhanced TILs proliferation and secretion of IFN-? and TNF-a. Conclusion Expression of Tim-3 and/or PD-1 on TILs impairs their function and correlates negatively with disease-free survival in HBV-HCC. Direct blockade of Tim-3 and PD-1 restores anti-tumor effects of TILs, which suggests a potential target for novel immunotherapy in HBV-HCC.

Dendritic cells (DCs) are professional antigen-presenting cells and initial stimulators for immune response. DCs can shape their functions based on their immune states, which are crucial for the balance of immunity and tolerance to preserve homeostasis. In the immune response involved in stem cell transplantation, DCs also play important roles in inducing immune tolerance and antitumor immunity. After the rapid development of stem cell transplantation technology in recent years, the risks of graft rejection, tumor recurrence, and tumorigenicity are still present after stem cell transplantation. It is important to understand the mechanisms of DC-mediated immune tolerance and stimulation during stem cell transplantation. In this review, we will summarize and analyze the regulatory mechanisms of DCs in stem cell transplantation and their application in clinical settings. It may help to promote the innovation in basic theories and therapeutic approaches of stem cell transplantation.

BACKGROUND The relationship between the clearance rate of ICG (indocyanine green) and varying degrees of liver fatty degeneration remains to be explored. The value of ICG detection in the evaluation of early prognosis following hepatic transplantation has been rarely investigated. MATERIAL AND METHODS Clinical data of 106 patients undergoing liver transplantation were retrospectively analyzed. The severity of fatty degeneration of the resected liver specimens was assessed by pathological biopsy. All patients were assigned into one of three groups: A (no fatty degeneration), B (

Somatic cells can be successfully reprogrammed into pluripotent stem cells by the ectopic expression of defined transcriptional factors. However, improved efficiency and better understanding the molecular mechanism underlying reprogramming are still required. In the present study, a scrape loading/dye transfer assay showed that human induced pluripotent stem cells (hiPSCs) contained functional gap junctions partially contributed by Connexin 45 (CX45). We then found CX45 was expressed in human embryonic stem cells (hESCs) and human dermal fibroblasts (hDFs) derived hiPSCs. Then we showed that CX45 was dramatically upregulated during the reprogramming process. Most importantly, the ectopic expression of CX45 significantly enhanced the reprogramming efficiency together with the Yamanaka factors (OCT4, SOX2, KLF4, cMYC - OSKM), whereas knockdown of endogenous CX45 expression significantly blocked cellular reprogramming and reduced the efficiency. Our further study demonstrated that CX45 overexpression or knockdown modulated the cell proliferation rate which was associated with the reprogramming efficiency. In conclusion, our data highlighted the critical role of CX45 in reprogramming and may increase the cell division rate and result in an accelerated kinetics of iPSCs production.

Introduction Prophylactic administration of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs) is the standard treatment for controlling hepatitis B virus (HBV) recurrence after liver transplantation (LT). Since lifelong use of HBIG is expensive and inconvenient and the antibodies level in anti-hepatitis B surface (HBs) is not sustainable and stable, an alternative strategy is to produce anti-HBs antibodies by active immunization. Our present study aimed to prospectively investigate the efficacy and safety of procedural HBV vaccination in transplanted patients. Methods Recipients who had undergone LT for hepatitis B related liver diseases more than one year before, with no evidence of HBV recurrence or rejection and normal liver function were enrolled. All subjects received the hepatitis B vaccine (40 μg) by intramuscular injection at months 0, 1, 2, 6 and 12 after enrollment with continuous administration of NAs. The liver function and anti-HBs titers were measured before each vaccination and HBIG (400U) was administrated intramuscularly when anti-HBs titer was lower than 30 IU/L during the course. The results of routine blood tests, liver function, concentration of immunosuppressant, and HBV-DNA copies were monitored during the research. After completion of the vaccination procedure, recipients were regarded as responders if their anti-HBs greater than 30 IU/L were maintained for up to six months without using HBIG and vaccine. Results Twenty-seven patients were enrolled in this study and the average anti-HBs titer before vaccination was 19.86±14.80 IU/L. The average anti-HBs titer of the nine responders at the end of the follow-up was 57.14±22.75 IU/L, giving an overall response rate of 33.3% (9/27). There were no reports of reactivation of HBV, rejection, severe anaphylaxis or other adverse events. Responders and non-responders showed their significant difference in anti-HBs titers after the fourth vaccination (P15) while most responders (8/9, 88.89%) had low LY/EO rates at the beginning of vaccination (P = 0.019). Conclusions Active immunization is an effective, cost-saving, and safe method for the prevention of HBV reactivation in patients transplanted for hepatitis B virus related liver diseases. The LY/EO rate may be a valuable indicator in selecting potential recipients for vaccination.

To compare the survival results of liver transplantation with radical resection for klatskin tumor based on the published literatures.We retrieved Medline for articles on treatment of klatskin tumor published from January 1996 to December 2014, and choose the literatures including liver transplantation and radical resection. Review Manager 5. 0 software was used to perform the Meta-analysis of the extracted data.After performing meta-analysis of 11 studies including 676 patients, we found comparable patient survival rate between liver transplantation group and radical resection group (1-year RR:1. 00, 95% CI:0. 82 - 1. 23, P = 0. 97; 3-year RR:1. 15, 95% CI:0. 75 - 1. 77, P 0. 51, 5-year RR: 1. 37, 95% CI: 0. 74 - 2. 53, P = 0. 32, respectively). No statistical significance of overall survival rate were shown between this 2 groups whether in short-term or long-time, but the total survival trends show the long-time survival of LT group is better than that of RR group which has the potential longer survival time.Liver transplantation was equivalent to radical resection for klatskin tumor treatment in terms of patient survival, with potential higher long-term patient survival rate and lower recurrence. especially for the patients with unrespectable KT or insufficient liver function, LT is superior for clinical outcome.