METTL3/16-mediated m6A modification of ZNNT1 promotes hepatocellular carcinoma progression by activating ZNNT1/osteopontin/S100A9 positive feedback loop-mediated crosstalk between macrophages and tumour cells.

Macrophages are the major components of tumour microenvironment, which play critical roles in tumour development. N6-methyladenosine (m6A) also contributes to tumour progression. However, the potential roles of m6A in modulating macrophages in hepatocellular carcinoma (HCC) are poorly understood. Here, we identified ZNNT1 as an HCC-related m6A modification target, which was upregulated and associated with poor prognosis of HCC. METTL3 and METTL16-mediated m6A modification contributed to ZNNT1 upregulation through stabilizing ZNNT1 transcript. ZNNT1 exerted oncogenic roles in HCC. Furthermore, ZNNT1 recruited and induced M2 polarization of macrophages via up-regulating osteopontin (OPN) expression and secretion. M2 Macrophages-recruited by ZNNT1-overexpressed HCC cells secreted S100A9, which further upregulated ZNNT1 expression in HCC cells via AGER/NF-κB signaling. Thus, this study demonstrates that m6A modification activated the ZNNT1/OPN/S100A9 positive feedback loop, which promoted macrophages recruitment and M2 polarization, and enhanced malignant features of HCC cells. m6A modification-triggered ZNNT1/OPN/S100A9 feedback loop represents potential therapeutic target for HCC.

Ultrasound-Guided Human Islet Transplantation: Safety, Feasibility, and Efficacy Analysis.

RATIONALE AND OBJECTIVES: We aimed to analyze the safety, feasibility, and efficacy of human islet transplantation (IT) using ultrasound (US) throughout the entire procedure. MATERIALS AND METHODS: A total of 22 recipients (18 males; mean age 42.6 ± 17.5years) with 35 procedures were retrospective included. Under US guidance, percutaneous transhepatic portal catheterization was successfully performed through a right-sided transhepatic approach, and islets were infused into the main portal vein. Color Doppler and contrast-enhanced ultrasound were used to guide the procedure and monitor the complications. After infusion of the islet mass, the access track was embolized by embolic material. If hemorrhage persisted, US-guided radiofrequency ablation (RFA) was performed to stop bleeding. Factors that could affect the complication were analyzed. After transplantation, primary graft function was evaluated with a ß-score 1month after the last islet infusion. RESULTS: The technical success rates were 100% with a single puncture attempt. Six (17.1%) abdominal bleeding episodes were immediately stopped by US-guided RFA. No portal vein thrombosis were encountered. Dialysis (OR (Odd Ratio): 32.0; 95% CI: 1.561-656.054; and P = .025) was identified as a significant factor associated with bleeding. Primary graft function was optimal in eight patients (36.4%), suboptimal in 13 patients (59.1%), and poor in one patient (4.5%). CONCLUSION: In conclusion, whole-procedure US-guided IT is a safe, feasible, and effective method for diabetes. Complications are either self-limiting or manageable with noninvasive treatment.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

Generation of a human induced pluripotent stem cell line (SYSUTFi001-A) from infiltrating cytotoxic T cells in hepatocellular carcinoma (HCC).

In this study, we report a novel induced pluripotent stem cell (iPSC) line SYSUTFi001-A derived from cytotoxic T cells (CTLs) infiltrating in hepatocellular carcinoma (HCC), using an integrative Sendai virus vector. This pluripotent cell line shows a normal karyotype and can be redifferentiated to the rejuvenated CTLs targeted to HCC. The cell line SYSUTFi001-A can be further used to perform vitro and vivo anti-tumor assays and design future cell replacement therapies.

Integrative network analysis of circular RNAs reveals regulatory mechanisms for hepatic specification of human iPSC-derived endoderm.

BACKGROUND: Human-induced pluripotent stem cell (hiPSC)-derived functional hepatic endoderm (HE) is supposed to be an alternative option for replacement therapy for end-stage liver disease. However, the high heterogeneity of HE cell populations is still challenging. Hepatic specification of definitive endoderm (DE) is an essential stage for HE induction in vitro. Recent studies have suggested that circular RNAs (circRNAs) determine the fate of stem cells by acting as competing endogenous RNAs (ceRNAs). To date, the relationships between endogenous circRNAs and hepatic specification remain elusive. METHODS: The identities of DE and HE derived from hiPSCs were determined by qPCR, cell immunofluorescence, and ELISA. Differentially expressed circRNAs (DEcircRNAs) were analysed using the Arraystar Human circRNA Array. qPCR was performed to validate the candidate DEcircRNAs. Intersecting differentially expressed genes (DEGs) of the GSE128060 and GSE66282 data sets and the DEcircRNA-predicted mRNAs were imported into Cytoscape for ceRNA networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were involved in the enrichment analysis. Hepatic markers and Wnt/ß-catenin were detected in hsa_circ_004658-overexpressing cells by western blotting. Dual-luciferase reporter assays were used to evaluate the direct binding among hsa_circ_004658, miRNA-1200 and CDX2. DE cells were transfected with miR-1200 mimics, adenovirus containing CDX2, and Wnt/ß-catenin was detected by western blotting. RESULTS: hiPSC-derived DE and HE were obtained at 4 and 9 days after differentiation, as determined by hepatic markers. During hepatic specification, 626 upregulated and 208 downregulated DEcircRNAs were identified. Nine candidate DEcircRNAs were validated by qPCR. In the ceRNA networks, 111 circRNA-miRNA-mRNA pairs were involved, including 90 pairs associated with hsa_circ_004658. In addition, 53 DEGs were identified among the intersecting mRNAs of the GSE128060 and GSE66282 data sets and the hsa_circ_004658-targeted mRNAs. KEGG and GO analyses showed that the DEGs associated with hsa_circ_004658 were mainly enriched in the WNT signalling pathway. Furthermore, hsa_circ_004658 was preliminarily verified to promote hepatic specification, as determined by hepatic markers (AFP, ALB, HNF4A, and CK19) (p < 0.05). This promotive effect may be related to the inhibition of the Wnt/ß-catenin signalling pathway (detected by ß-catenin, p-ß-catenin, and TCF4) when hsa_circ_004658 was overexpressed (p < 0.05). Dual-luciferase reporter assays showed that there were binding sites for miR-1200 in the hsa_circ_004658 sequence, and confirmed the candidate DEG (CDX2) as a miR-1200 target. The level of miR-1200 decreased and the level of CDX2 protein expression increased when hsa_circ_004658 was overexpressed (p < 0.05). In addition, the results showed that CDX2 may suppress the Wnt/ß-catenin signalling during hepatic specification (p < 0.05). CONCLUSIONS: This study analysed the profiles of circRNAs during hepatic specification. We identified the hsa_circ_004658/miR-1200/CDX2 axis and preliminarily verified its effect on the Wnt/ß-catenin signalling pathway during hepatic specification. These results provide novel insight into the molecular mechanisms involved in hepatic specification and could improve liver development in the future.

Abrogation of graft ischemia-reperfusion injury in ischemia-free liver transplantation.

BACKGROUND: Ischemia-reperfusion injury (IRI) is considered an inherent component of organ transplantation that compromises transplant outcomes and organ availability. The ischemia-free liver transplantation (IFLT) procedure has been developed to avoid interruption of blood supply to liver grafts. It is unknown how IFLT might change the characteristics of graft IRI. METHODS: Serum and liver biopsy samples were collected from IFLT and conventional liver transplantation (CLT) recipients. Pathological, metabolomics, transcriptomics, and proteomics analyses were performed to identify the characteristic changes in graft IRI in IFLT. RESULTS: Peak aspartate aminotransferase (539.59 ± 661.76 U/L versus 2622.28 ± 3291.57 U/L) and alanine aminotransferase (297.64 ± 549.50 U/L versus 1184.16 ± 1502.76 U/L) levels within the first 7 days and total bilirubin levels by day 7 (3.27 ± 2.82 mg/dl versus 8.33 ± 8.76 mg/dl) were lower in the IFLT versus CLT group (all p values < 0.001). The pathological characteristics of IRI were more obvious in CLT grafts. The antioxidant pentose phosphate pathway remained active throughout the procedure in IFLT grafts and was suppressed during preservation and overactivated postrevascularization in CLT grafts. Gene transcriptional reprogramming was almost absent during IFLT but was profound during CLT. Proteomics analysis showed that "metabolism of RNA" was the major differentially expressed process between the two groups. Several proinflammatory pathways were not activated post-IFLT as they were post-CLT. The activities of natural killer cells, macrophages, and neutrophils were lower in IFLT grafts than in CLT grafts. The serum levels of 14 cytokines were increased in CLT versus IFLT recipients. CONCLUSIONS: IFLT can largely avoid the biological consequences of graft IRI, thus has the potential to improve transplant outcome while increasing organ utilization.

The predictive role of preoperative serum glutamate dehydrogenase levels in microvascular invasion and hepatocellular carcinoma prognosis following liver transplantation-a single center retrospective study.

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.

Ischaemia-free liver transplantation in humans: a first-in-human trial.

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<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach. Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers. Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology. Panel: Research in context.

Prediction of post-transplant graft survival by different definitions of early allograft dysfunction.

BACKGROUND: The efficacy of early allograft dysfunction (EAD) definitions in predicting post-transplant graft survival in a Chinese population is still unclear. METHODS: A total of 607 orthotopic liver transplants (OLT) have been included in the current study. Model accuracy was evaluated using receiver operating characteristic (ROC) analysis. Risk factors for EAD was evaluated using univariable analysis and multivariable logistic regression model. RESULTS: The 3-, 6-, and 12-month patient/graft survival were 91.6%/91.4%, 91.1%/90%, and 87.5%/87.3%, respectively. MELDPOD5 had a superior discrimination of 3-month graft survival (C statistic, 0.83), compared with MEAF (C statistic, 0.77) and Olthoff criteria (C statistic, 0.72). Multivariate analysis of risk factors for EAD defined by MELDPOD5, showed that donor body mass index (P=0.001), donor risk index (P=0.006), intraoperative use of packed red blood cells (P=0.001), hypertension of recipient (P=0.004), and preoperative total bilirubin (P<0.001) were independent risk factors. CONCLUSIONS: The results suggest that MLEDPOD5 is a better criterion of EAD for the Chinese population, which might serve as a surrogate end-point for graft survival in clinical study.

Two case reports of rare diseases occurring in rare parts: splenic vein solitary fibrous tumor and liver solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare soft tissue tumor originating from mesenchymal cells. Here we report two new cases of SFT. One case was a 37-year-old female patient whose primary tumor site was located in the splenic vein and the primary tumor resulted in splenomegaly and hypersplenism; its recurred for many times after surgical resection and eventually transferred to the liver, 4 operations were performed during 10 years of follow-up, and the patient 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. We performed two operations to remove these tumors, totally. Six years later, SFT recurred in the liver, given that the tumor was too large to be surgical resected completely, we chose orthotopic liver transplantation (OLT), and no tumor recurred during 6 years' follow-up, he is also in a good condition right now. The reports of these two cases of SFT are exceedingly rare, especially the splenic vein SFT is the first report case, which helps expand the understanding of SFT. Although the current mainstream treatment of SFT is surgical resection, liver transplantation may be a new option treatment for the huge liver SFT.

Correction: A Novel Approach to Assessing Differentiation Degree and Lymph Node Metastasis of Extrahepatic Cholangiocarcinoma: Prediction Using a Radiomics-Based Particle Swarm Optimization and Support Vector Machine Model.

[This corrects the article DOI: 10.2196/23578.].

Avoiding Ischemia Reperfusion Injury in Liver Transplantation.

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.

Outcomes of Combined Liver and Pancreas Transplantation: A Review of the SRTR National Database and a Report of the Largest Single Center Series.

Purposes: This study was intended to summarize the characteristics and clinical outcome of Liver and Pancreas (LPTx) recipients in the Scientific Registry of Transplant Recipients (SRTR) database vs. the largest series from the First Affiliated Hospital (FAH), Sun Yat-sen University. Methods: The clinical data of 23 patients who underwent LPTx from 2000 to 2016 in the United States and 31 patients who underwent modified LPTx procedure (known as simplified multivisceral transplantation [SMT]) from 2008 to 2017 in our center were reviewed. The indications, surgical techniques, patient and graft survival, and complications were compared between the two groups. Results: All recipients in the FAH group were diagnosed with type 2 diabetes mellitus, while 10 of 23 recipients were diagnosed with type 1 diabetes mellitus in the SRTR group. The 1-, 3-, and 5-year cumulative patient survival rates were 81, 74, and 74% in the FAH group, respectively, and 51, 47, and 37% in the SRTR group, respectively (P = 0.023). No diabetes was observed during follow-up in the FAH group, while the diabetes recurrence rate was 22.2% in the SRTR group (P = 0.03). Conclusion: With multiple techniques modified and indications changed, the SMT procedure yielded a preferable outcome compared to that of the traditional LPTx procedure in records of SRTR. SMT has become a treatment option for patients with end-stage liver disease and concurrent diabetes.

A Novel Approach to Assessing Differentiation Degree and Lymph Node Metastasis of Extrahepatic Cholangiocarcinoma: Prediction Using a Radiomics-Based Particle Swarm Optimization and Support Vector Machine Model.

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.

Association of Perfusion Characteristics and Posttransplant Liver Function in Ischemia-Free Liver Transplantation.

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.

Prospective, single-centre, randomised controlled trial to evaluate the efficacy and safety of ischaemia-free liver transplantation (IFLT) in the treatment of end-stage liver disease.

INTRODUCTION: During 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 ANALYSIS: This 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 DISSEMINATION: The 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 NUMBER: ChiCTR1900021158.

Systematic Evaluation of Research Progress on Natural Language Processing in Medicine Over the Past 20 Years: Bibliometric Study on PubMed.

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.

Outcome of the use of paediatric donor livers in adult recipients: A single Chinese centre experience.

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.