p-d Orbital Hybridization-Engineered PdSn Nanozymes for a Sensitive Immunoassay.

Nanozymes with peroxidase-like activity have been extensively studied for colorimetric biosensing. However, their catalytic activity and specificity still lag far behind those of natural enzymes, which significantly affects the accuracy and sensitivity of colorimetric biosensing. To address this issue, we design PdSn nanozymes with selectively enhanced peroxidase-like activity, which improves the sensitivity and accuracy of a colorimetric immunoassay. The peroxidase-like activity of PdSn nanozymes is significantly higher than that of Pd nanozymes. Theoretical calculations reveal that the p-d orbital hybridization of Pd and Sn not only results in an upward shift of the d-band center to enhance hydrogen peroxide (H2O2) adsorption but also regulates the O-O bonding strength of H2O2 to achieve selective H2O2 activation. Ultimately, the nanozyme-linked immunosorbent assay has been successfully developed to sensitively and accurately detect the prostate-specific antigen (PSA), achieving a low detection limit of 1.696 pg mL-1. This work demonstrates a promising approach for detecting PSA in a clinical diagnosis.

International Multicenter Study of Ultra-Low GRWR Grafts in Adult Living Donor Liver Transplantation.

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient-weight-ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multi-center study, 92 adult LDLT with a final GRWR<=0.6 performed at 12 international liver transplant (LT) centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation (PFM), development of SFSS, morbidity and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day and one-year mortality. Pre-operative MELD and inpatient status were independent predictors for SFSS (p<0.05). Pre-LT renal dysfunction was an independent predictor of survival (Hazard ratio- 3.1;95% ci 1.1,8.9, p=0.035). PFH or PFM were not predictive of SFSS or survival. We report the largest ever multi-center study of LDLT outcomes using ultralow-GRWR grafts and for the first-time validate the ILTS-iLDLT-LTSI consensus definition and grading of SFSS. Pre-operative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

Pretransplant use of immune checkpoint inhibitors for hepatocellular carcinoma: A multicenter, retrospective cohort study.

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

Elevating Lithium-Sulfur Battery Durability through Samarium Oxide/Ketjen Black Modified Separator.

Lithium-sulfur batteries have garnered significant attention as a promising next-generation battery technology due to their potential for high energy density. However, their practical application is hampered by slow reaction kinetics and the shuttle effect of lithium polysulfide intermediates. In this context, the authors introduce a pioneering solution in the form of a novel porous carbon nanostructure modified with samarium oxide, denoted as Sm2O3/KB. The material has a highly polar surface, allowing lithium polysulfide to be chemisorbed efficiently. The unsaturated sites provided by the oxygen vacancies of Sm2O3 promote Li2S nucleation, lowering the reaction energy barrier and accelerating Li2S dissolution. The porous structure of Ketjen Black provides a highly conductive channel for electron transport and effectively traps polysulfides. Meanwhile, the batteries with Sm2O3/KB/PP spacers exhibited remarkable electrochemical performances, including a low-capacity decay rate of only 0.046 % for 1000 cycles at 2 C and an excellent multiplicative performance of 624 mAh g-1 at 3 C. This work opens up a new avenue for the potential use of rare-earth-based materials in lithium-sulfur batteries.

Quantification of Serum Metabolites in Early Colorectal Adenomas Using Isobaric Labeling Mass Spectrometry.

A major challenge in reducing the death rate of colorectal cancer is to screen patients using low-invasive testing. A blood test shows a high compliance rate with reduced invasiveness. In this work, a multiplex isobaric tag labeling strategy coupled with mass spectrometry is adopted to relatively quantify primary and secondary amine-containing metabolites in serum for the discovery of metabolite level changes of colorectal cancer. Serum samples from patients at different risk statuses and colorectal cancer growth statuses are studied. Metabolite identification is based on accurate mass matching and/or retention time of labeled metabolite standards. We quantify 40 metabolites across all the serum samples, including 18 metabolites validated with standards. We find significantly decreased levels of threonine and asparagine in the patients with growing adenomas or high-risk adenomas (p < 0.05). Glutamine levels decrease in patients with adenomas of unknown growth status or high-risk adenomas. In contrast, arginine levels are elevated in patients with low-risk adenoma. Receiver operating characteristic analysis shows high sensitivity and specificity of these metabolites for detecting growing adenomas. Based on these results, we conclude that a few metabolites identified here might contribute to distinguishing colorectal patients with growing adenomas from normal individuals and patients with unknown growth status of adenomas.

Single-Atom Indium Boosts Electrochemical Dopamine Sensing.

A rational design of high-efficiency electrocatalysts and thus achieving sensitive electrochemical sensing remains a great challenge. In this work, single-atom indium anchored on nitrogen-doped carbon (In1-N-C) with an In-N4 configuration is prepared successfully through a high-temperature annealing strategy; the product can serve as an advanced electrocatalyst for sensitive electrochemical sensing of dopamine (DA). Compared with In nanoparticle catalysts, In1-N-C exhibits high catalytic performance for DA oxidation. The theoretical calculation reveals that In1-N-C has high adsorption energy for hydroxy groups and a low energy barrier in the process of DA oxidation compared to In nanoparticles, indicating that In1-N-C with atomically dispersed In-N4 sites possesses enhanced intrinsic activity. An electrochemical sensor for DA detection is established as a concept application with high sensitivity and selectivity. Furthermore, we also verify the feasibility of In1-N-C catalysts for the simultaneous detection of uric acid, ascorbic acid, and DA. This work extends the application prospect of p-block metal single-atom catalysts in electrochemical sensing.

CHRISTMAS: Chiral Pair Isobaric Labeling Strategy for Multiplexed Absolute Quantitation of Enantiomeric Amino Acids.

Amino acids (AAs) in the d-form are involved in multiple pivotal neurological processes, although their l-enantiomers are most commonly found. Mass spectrometry-based analysis of low-abundance d-AAs has been hindered by challenging enantiomeric separation from l-AAs, low sensitivity for detection, and lack of suitable internal standards for accurate quantification. To address these critical gaps, N,N-dimethyl-l-leucine (l-DiLeu) tags are first validated as novel chiral derivatization reagents for chromatographic separation of 20 pairs of d/l-AAs, allowing the construction of a 4-plex isobaric labeling strategy for enantiomer-resolved quantification through single step tagging. Additionally, the creative design of N,N-dimethyl-d-leucine (d-DiLeu) reagents offers an alternative approach to generate analytically equivalent internal references of d-AAs using d-DiLeu-labeled l-AAs. By labeling cost-effective l-AA standards using paired d- and l-DiLeu, this approach not only enables absolute quantitation of both d-AAs and l-AAs from complex biological matrices with enhanced precision but also significantly boosts the combined signal intensities from all isobaric channels, greatly improving the detection and quantitation of low-abundance AAs, particularly d-AAs. We term this quantitative strategy CHRISTMAS, which stands for chiral pair isobaric labeling strategy for multiplexed absolute quantitation. Leveraging the ion mobility collision cross section (CCS) alignment, interferences from coeluting isomers/isobars are effectively filtered out to provide improved quantitative accuracy. From wild-type and Alzheimer's disease (AD) mouse brains, we successfully quantified 20 l-AAs and 5 d-AAs. The significant presence and differential trends of certain d-AAs compared to those of their l-counterparts provide valuable insights into the involvement of d-AAs in aging, AD progression, and neurodegeneration.

Single-Site SnOCu Pairs with Interfacial Electron Transfer Effect for Enhanced Electrochemical Catalysis and Sensing.

As advanced electrochemical catalysts, single-atom catalysts have made great progress in the field of catalysis and sensing due to their high atomic utilization efficiency and excellent catalytic performance. Herein, stannum-doped copper oxide (CuOSn1 ) nanosheets with single-site SnOCu pairs as active sites are synthesized as electrocatalysts for biological molecule detection. Compared with CuO-based electrochemical sensors, the CuOSn1 -based electrochemical sensors have improved detection sensitivity with a rapid electrochemical response. Theoretical calculation reveals that the single-site SnOCu pairs induced interfacial electronic transfer effect can strengthen hydroxy adsorption and thus reduce the energy barrier of the biological molecule oxidation process. As a concept application, electrochemical detection of dopamine and uric acid molecules is achieved, exhibiting satisfactory sensitivity and selectivity. This work demonstrates the advantages of single-site SnOCu pairs in electrochemical catalysis and sensing, which provides theoretical guidance for understanding the structure-activity relationship for sensitive electrochemical sensing.

A novel approach of intraoperative cholangiography in laparoscopic left lateral sectionectomy in living donor liver transplantation.

BACKGROUND: Accurate division of bile duct during laparoscopic donor hepatectomy in living donor liver transplantation is essential. We here present a novel approach to achieve cholangiography via the bile duct stump of segment IV (B4 stump) during laparoscopic donor hepatectomy in adult-to-pediatric living donor liver transplantation. PATIENTS AND METHODS: Donors who underwent laparoscopic left lateral sectionectomy (LLLS) from January 2022 to April 2022 in our liver transplant center were retrospectively analyzed. A total of 32 donors were eventually enrolled into this study. Cholangiography via the B4 stump was performed in 11 donors (B4 group) while indocyanine green (ICG) fluorescence guiding was performed in 21 donors (ICG group). Perioperative data were collected and compared between groups. RESULTS: Cholangiography by catheterizing the B4 stump was successfully performed in all 11 donors in the B4 group. The mean time of this procedure was 12.82 ± 9.11 min. Compared to the ICG group, it was more likely to acquire single bile duct orifice on graft in the B4 group (B4: 10/11, 90.91% vs ICG: 9/21, 42.86%) and it was significantly different (p = 0.030). The donors' complications (Clavien-Dindo grade III-IV) were not significantly different. There was one donor developed intraperitoneal effusion in B4 group, while two donors (one bile leakage and one biliary stricture) developed biliary tract related complications in the ICG group. A Roux-en-Y was performed to solve the biliary stricture in the ICG group. The recipients' outcomes were not significantly different between groups. CONCLUSIONS: Cholangiography via the B4 stump catheterization is feasible and safe in identifying the bifurcation of bile duct during LLLS.

Progress in Hybridization of Covalent Organic Frameworks and Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) hybrid materials are a class of porous crystalline materials that integrate MOFs and COFs with hierarchical pore structures. As an emerging porous frame material platform, MOF/COF hybrid materials have attracted tremendous attention, and the field is advancing rapidly and extending into more diverse fields. Extensive studies have shown that a broad variety of MOF/COF hybrid materials with different structures and specific properties can be synthesized from diverse building blocks via different chemical reactions, driving the rapid growth of the field. The allowed complementary utilization of π-conjugated skeletons and nanopores for functional exploration has endowed these hybrid materials with great potential in challenging energy and environmental issues. It is necessary to prepare a "family tree" to accurately trace the developments in the study of MOF/COF hybrid materials. This review comprehensively summarizes the latest achievements and advancements in the design and synthesis of MOF/COF hybrid materials, including COFs covalently bonded to the surface functional groups of MOFs (MOF@COF), MOFs grown on the surface of COFs (COF@MOF), bridge reaction between COF and MOF (MOF+COF), and their various applications in catalysis, energy storage, pollutant adsorption, gas separation, chemical sensing, and biomedicine. It concludes with remarks concerning the trend from the structural design to functional exploration and potential applications of MOF/COF hybrid materials.

Impact of the Kasai Procedure and the Length of Native Liver Survival Time on Outcomes of Liver Transplantation for Biliary Atresia.

The aim is to explore the impact of the Kasai procedure (KP) and the length of native liver survival time (NLST) on outcomes of liver transplantation (LT). Patients with biliary atresia (BA), who underwent LT in Beijing Friendship Hospital from January 2017 to December 2019, were enrolled and divided into non-KP (N-KP) and post-KP (P-KP) groups. The patients in the P-KP group were further divided into early failure (KP-EF) defined by NLST <1 year, medium failure (KP-MF, NLST 1-5 years), and late failure (KP-LF, NLST >5 years) subgroups. Clinical data at baseline and during follow-up were collected. The inverse probability of treatment weighting method was used to evaluate the independent effect of KP and the length of NLST on clinical outcomes. Among 197 patients with BA, the N-KP group accounted for 43 (21.8%), KP-EF 71 (46.1%), KP-MF 59 (38.3%), and KP-LF 24 (15.6%) cases, respectively. The N-KP and KP-EF groups had significantly longer hospitalization and intensive care unit stays after LT. Graft and overall survival rates were 93.0% in the N-KP group and 97.4% in P-KP group, respectively. The mortality rate in the P-KP group were significantly lower compared with that of the N-KP group with a hazard ratio (HR) of 0.2 (P = 0.02). The risks of biliary and vascular complications and cytomegalovirus (CMV) infection after LT were significantly higher in KP-EF group than those in the KP-MF and KP-LF groups (HRs = 0.09, 0.2, and 0.3, respectively; all P < 0.001). The KP significantly improved after LT overall survival. Patients with early native liver failure after KP have significantly higher risks for biliary and vascular complications and CMV infection.

Domino hepatocyte transplantation using explanted human livers with metabolic defects attenuates D-GalN/LPS-induced acute liver failure.

BACKGROUND: Explanted livers from patients with inherited metabolic liver diseases possess the potential to be a cell source of good-quality hepatocytes for hepatocyte transplantation (HT). This study evaluated the therapeutic effects of domino HT using hepatocytes isolated from explanted human livers for acute liver failure (ALF). METHODS: Isolated hepatocytes were evaluated for viability and function and then transplanted into D-galactosamine/lipopolysaccharide-induced ALF mice via splenic injection. The survival rate was analyzed by the Kaplan-Meier method and log-rank test. Liver function was evaluated by serum biochemical parameters, and inflammatory cytokine levels were measured by ELISA. The pathological changes in the liver tissues were assessed by hematoxylin-eosin staining. Hepatocyte apoptosis was investigated by TUNEL, and hepatocyte apoptosis-related proteins were detected by western blot. The localization of human hepatocytes in the injured mouse livers was detected by immunohistochemical analyses. RESULTS: Hepatocytes were successfully isolated from explanted livers of 10 pediatric patients with various liver-based metabolic disorders, with an average viability of 85.3% ± 13.0% and average yield of 9.2 × 106 ± 3.4 × 106 cells/g. Isolated hepatocytes had an excellent ability to secret albumin, produce urea, uptake indocyanine green, storage glycogen, and express alpha 1 antitrypsin, albumin, cytokeratin 18, and CYP3A4. Domino HT significantly reduced mortality, decreased serum levels of alanine aminotransferase and aspartate aminotransferase, and improved the pathological damage. Moreover, transplanted hepatocytes inhibited interleukin-6 and tumor necrosis factor-α levels. Domino HT also ameliorates hepatocyte apoptosis, as evidenced by decreased TUNEL positive cells. Positive staining for human albumin suggested the localization of human hepatocytes in ALF mice livers. CONCLUSION: Explanted livers from patients with inheritable metabolic disorders can serve as a viable cell source for cell-based therapies. Domino HT using hepatocytes with certain metabolic defects has the potential to be a novel therapeutic strategy for ALF.

High-throughput circular RNA sequencing reveals the profiles of circular RNA in non-cirrhotic hepatocellular carcinoma.

BACKGROUND: Liver cirrhosis is a well-known risk factor for hepatocellular carcinoma (HCC). However, some HCC cases can also originate from non-cirrhotic livers. The aim of this study was to identify key circular RNAs (circRNAs) associated with the tumorigenesis of non-cirrhotic liver disease. METHODS: The differently expressed circRNAs between non-cirrhotic and cirrhotic HCCs were assessed with use of high-throughput circRNAs sequencing and validated with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Potential biological functions of these dysregulated circRNAs were predicted with use of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A circRNA-miRNA-mRNA regulation network was constructed as achieved with use of miRanda software and visualized using Cytoscape software. Biological functions of the four most prominent dysregulated circRNAs identified were confirmed by in vitro experiments. Moreover, possible translations of these dysregulated circRNAs were also predicted. RESULTS: A total of 393 dysregulated circRNAs were identified between non-cirrhotic and cirrhotic HCC, including 213 that were significantly up-regulated and 180 significantly down-regulated circRNAs. Expression levels of the six most prominent dysregulated circRNAs were further validated using qRT-PCR. Many tumor related miRNAs were involved in the circRNA-miRNA-mRNA networks, including miR-182-5p, miR-561-3p, miR-125a-5p, miR-145, miR-23b-3p and miR-30e-3p, and downstream mRNAs of dysregulated circRNAs were significantly related with biological processes involved in the progression of tumors, including proliferation, migration, differentiation, and focal adhesion. Results from the in vitro experiments demonstrated that the most prominent dysregulated circRNAs exerted notable effects upon the proliferation and migration of HCC cells. Finally, we also identified 19 dysregulated circRNAs having potential for the coding of functional peptides. CONCLUSION: The results of this present study indicate that circRNAs may play important roles in tumorigenesis of non-cirrhotic HCC. Such findings provide some novel insights and pave the way for the development of future studies directed at investigating the initiation and treatment of HCC.

Elevated effluent potassium concentrations predict the development of postreperfusion hyperkalemia in deceased liver transplantation: a retrospective cohort study.

BACKGROUND: Postreperfusion hyperkalemia (PRHK) has garnered increasing attention in regard to deceased liver transplantation (LT), especially for LT using the expanded criteria donor grafts. However, the impact of the effluent potassium (eK+) concentration on PRHK has been largely overlooked. We evaluated whether elevated eK+ concentrations are associated with PRHK in deceased LT. METHODS: In this single-institution, retrospective cohort study, we included all adults who underwent deceased LT with intraoperative eK+ concentration monitoring between November 2016 and December 2018. The eK+ concentrations were obtained from the effluent samples collected following a standard portal vein flush. PRHK was defined as any serum potassium (sK+) level of > 5.5 mmol/L following reperfusion. Logistic regression was performed to identify predictors for PRHK, and linear regression was used to examine predictors of the maximum percentage increase in the sK+ level following reperfusion. RESULTS: Of the 86 patients who met the inclusion criteria, 54 (62.8%) developed PRHK. Independent predictors for PRHK included greater graft weight (OR 1.283 [95% CI 1.029-1.599] per 100 g, P = 0.027), an elevated eK+ concentration (OR 1.291 [95% CI 1.068-1.561] per mol/L, P = 0.008), and a higher sK+ level before reperfusion (OR 4.459 [95% CI 1.543-12.884] per mol/L, P = 0.006). An eK+ concentration of more than 6.9 mmol/L had a sensitivity of 59.26% and a specificity of 78.12% for predicting PRHK (area under the receiver operating characteristic curve, 0.694). Multiple linear regression analyses indicated that the eK+ and sK+ levels before reperfusion were significant predictors of the maximum percentage increase in the sK+ level following reperfusion. In addition, PRHK was associated with an increased risk of postreperfusion significant arrhythmias, severe postreperfusion syndrome, and postoperative early allograft dysfunction. CONCLUSIONS: This study shows that the eK+ concentration could predict the risk of PRHK in deceased LT. Further prospective studies are warranted to clarify these associations.

Marginal parental donors for pediatric living donor liver transplantation.

PURPOSE OF REVIEW: Living donor liver transplantation (LT) has been increasingly recognized as an effective treatment modality with excellent patient survival. Indications for LT have evolved not only for cholestatic liver disease, but also metabolic liver diseases. Living donor selection, particularly for pediatric inherited disease, is essential to prevent morbidity, both in the donor and recipient. RECENT FINDINGS: Based on 30 years of experience in pediatric living donor LT in Japan, we could identify marginal parental living donors who have potential risks following LT, including heterozygous mothers with ornithine transcarbamylase deficiency, heterozygous protein C deficiency, heterozygous hypercholesterolemia, heterozygous protoporphyria, asymptomatic parental donors with paucity of intrahepatic bile duct, and human leukocyte antigen-homozygous parental donors. SUMMARY: Although these situations seem rare due to infrequency of the condition, careful living donor evaluation is required to optimize the outcomes for pediatric recipients. In the setting of an appropriate selection of a living donor, we should avoid any additional hazards, given that the procedure itself has risks for a healthy individual.

Perioperative Management and Clinical Outcomes of Liver Transplantation for Children with Homozygous Familial Hypercholesterolemia.

Background and Objectives: Liver transplantation (LT) has been accepted as a life-saving option as a last resort for children with homozygous familial hypercholesterolemia (HoFH). Perioperative management of LT for HoFH poses extra challenges for clinicians largely due to premature atherosclerotic cardiovascular diseases (ASCVDs). We aimed to analyze our data of pediatric LT recipients with HoFH, with special attention paid to perioperative management and clinical outcomes. Materials and Methods: After obtaining approval from the local ethics committee, the clinical data of pediatric patients with HoFH who underwent LT at our institution between January 2014 and February 2021 were retrospectively studied. Results: Six pediatric LT recipients with HoFH were included in the analysis. Although ASCVDs were common before LT, all children with HoFH survived the perioperative period without in-hospital mortality. However, one patient experienced acute myocardial infarction two months following LT and was successfully treated with medical interventions. Post-LT metabolic improvement was shown by declines in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in the early post-LT period (for TC: 14.7 ± 3.2 mmol/L vs. 5.5 ± 1.8 mmol/L, p < 0.001; for LDL-C: 10.6 ± 2.2 mmol/L vs. 3.6 ± 1.2 mmol/L, p < 0.001, respectively) and at the last follow-up (for TC: 14.7 ± 3.2 mmol/L vs. 4.5 ± 0.9 mmol/L, p = 0.001; for LDL-C: 10.6 ± 2.2 mmol/L vs. 2.8 ± 0.6 mmol/L, p = 0.001, respectively). Dietary restrictions could be lifted after LT. However, three patients required restarting lipid-lowering therapy after LT due to suboptimal LDL-C levels and progression of ASCVDs. Conclusions: Our data suggest that LT can be a safe and feasible therapeutic option for well-selected patients with HoFH, offering relaxed dietary restrictions and remarkable reductions in LDL-C levels. However, concerns remain regarding progression of ASCVDs after LT.

Early transjugular intrahepatic portosystemic shunt for acute variceal bleeding: a systematic review and meta-analysis.

OBJECTIVES: The alleged benefit of early placement of transjugular intrahepatic portosystemic shunt (TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) remains controversial. This meta-analysis was conducted to evaluate the therapeutic effect of early TIPS on cirrhotic patients with AVB. METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for relevant literatures. Data from included studies were extracted, and random-effects meta-analyses were performed. RESULTS: Three randomized control trials and six observational studies involving 2878 participants were included. Compared with those undergoing standard treatment, patients undergoing early TIPS had a significantly lower all-cause mortality (RR, 0.64; 95% CI, 0.52-0.79). Furthermore, early TIPS was associated with a significantly reduced incidence of failure to control bleeding (RR, 0.15; 95% CI, 0.07-0.29) and rebleeding (RR, 0.40; 95% CI, 0.23-0.71), without increasing the risk of hepatic encephalopathy (RR, 1.13; 95% CI, 0.92-1.38). In a stratification analysis based on Child-Pugh classification, the survival benefit was observed in Child-Pugh B patients with active bleeding (RR, 0.53; 95% CI, 0.31-0.93) and Child-Pugh C patients (RR 0.55, 95% CI, 0.37-0.82), but not in low-risk patients (Child-Pugh A and Child-Pugh B without active bleeding) (RR, 0.93; 95% CI, 0.55-1.57). CONCLUSION: Early TIPS is a feasible therapeutic option for cirrhotic patients with AVB, especially benefiting high-risk patients in terms of improved survival. Given the current low utilization rate in clinical practice, this study favors the placement of early TIPS in a wider range of patients with cirrhosis and AVB, especially high-risk patients. KEY POINTS: • Early TIPS is associated with improved survival in high-risk patients (Child-Pugh B plus active bleeding at endoscopy or Child-Pugh C 10-13) with cirrhosis and acute variceal bleeding. • Current utilization rate of early TIPS is low in clinical practice.

Assessment of breast arteries and lymph nodes by 3D MR angiography enhancement imaging: feasibility and pilot clinical results.

BACKGROUND: Conventional dynamic contrast enhanced (DCE) magnetic resonance (MR) hardly achieves a good imaging performance of arteries and lymph nodes in the breast area. Therefore, a new imaging method is needed for the assessment of breast arteries and lymph nodes. METHODS: We performed prospective research. The research included 52 patients aged from 25 to 64 between June 2019 and April 2020. The isotropic e-THRIVE sequence scanned in the coronal direction after DCE-THRIVE. Reconstructed images obtained by DCE-THRIVE and the coronal e-THRIVE were compared mainly in terms of the completeness of the lateral thoracic artery, thoracodorsal artery, and lymph nodes. We proposed a criterion for evaluating image quality. According to the criterion, images were assigned a score from 1 to 5 according to the grade from low to high. Two board-certified doctors evaluated images individually, and their average score was taken as the final result. The chi-square test was used to assess the difference. RESULTS: The coronal e-THRIVE score is 4.60, which is higher than the DCE-THRIVE score of 3.48, there are significant differences between the images obtained by two sequences (P = 1.2712e-8). According to the score of images, 44 patients (84.61%) had high-quality images on the bilateral breast. Only 3 patients' (5.77%) images were not ideal on both sides. The improved method is effective for most patients to get better images. CONCLUSIONS: The proposed coronal e-THRIVE scan can get higher quality reconstruction images than the conventional method to visualize the course of arteries and the distribution of lymph nodes in most patients, which will be helpful for the clinical follow-up treatment.

Post-transplant lymphoproliferative disorder after paediatric liver transplantation.

OBJECTIVE: The purpose of this study was to analyse the clinical and pathological characteristics, treatments and outcomes of post-transplant lymphoproliferative disorder (PTLD) in paediatric liver transplant recipients. METHOD: A retrospective analysis of records from nine paediatric liver transplant recipients with PTLD who were treated at our Liver Transplant Center over the period from June 2013 to August 2018. RESULT: Of these nine patients, seven received liver transplantation in our centre and the remaining two patients at other hospitals. The overall incidence of PTLD in paediatric liver transplant recipients in our centre was 1.4% (7/485). The median onset of PTLD after liver transplantation was 11 months. Three cases were classified as infectious mononucleosis PTLD, one case was plasmacytic hyperplasia PTLD, one case was polymorphic PTLD and two cases were Burkitt lymphoma. One case showed diffuse large B-cell lymphoma and one was classical Hodgkin lymphoma-like PTLD. These patients presented with different clinical manifestations including fever, anaemia, diarrhoea, hypoproteinaemia, enlargement of lymph nodes, hepatosplenomegaly, jaundice, bowel obstruction and even intestinal perforation. Nine patients were positive for EBV-DNA in serum. After diagnosis, immunosuppressants were reduced or discontinued in all cases. Eight patients received anti-CD20 monoclonal antibody (Rituximab) therapy, four cases were treated with a combination of chemotherapy (R-CHOP, ABVD, COPP/ABV) and one case was combined with radiotherapy. Two cases received surgical treatment due to bowel obstruction. Eight of these patients achieved a complete remission and remained healthy when assessed at the time of final follow-up. One patient died as a result of PTLD progression. CONCLUSION: PTLD is one of the most serious and fatal complications after liver transplantation. The definitive diagnosis requires histopathology. Treatment varies and basically includes immunosuppression reduction, anti-CD20 antibody, surgery, radiotherapy and chemotherapy.

Mycophenolate mofetil enhances the effects of tacrolimus on the inhibitory function of regulatory T cells in patients after liver transplantation via PD-1 and TIGIT receptors.

OBJECTIVE: Regulatory T cells (Tregs) induce immune tolerance in patients after organ transplantation. Various immunosuppressors can affect Tregs function through different mechanisms. PD-1 and TIGIT are important receptors on Tregs surface. Here, we investigated the effects of Tacrolimus and mycophenolate mofetil (MMF) on the inhibitory function of Tregs and explored the regulatory mechanism in patients after liver transplantation. METHODS: Thirty patients that underwent a liver transplant and 15 healthy people were enrolled. Fifteen patients received Tacrolimus only, and 15 received a combination of Tacrolimus and MMF. Tregs and effector T cells (Teffs) were isolated using magnetic beads and were mixed at different ratios of 0:1, 1:4, 1:2 and 1:1. An inhibition assay was performed by adding anti-PD-1 and anti-TIGIT when the mixture ratio was 1:1. The Tregs inhibition rate was determined and the levels of IFN-γ and TNF-α were measured. RESULTS: As the ratios of Tregs to Teffs in the mixture increased, the Tregs inhibition rate increased and the levels of IFN-γ and TNF-α decreased. At each mixture ratio, Tacrolimus + MMF group had the highest Tregs inhibition rate compared to Tacrolimus and control group. At the specific mixture ratio of 1:1, the addition of both anti- PD-1 and anti-TIGIT led to lower Tregs inhibition rate and higher IFN-γ and TNF-α levels in all three groups as opposed to the addition of each antibody separately. Additionally, both the decrease in the Tregs inhibition rate and the increase in the IFN-γ and TNF-α levels were the most for Tacrolimus + MMF group among all cases, either adding antibodies alone or mixed. CONCLUSION: Tacrolimus and MMF enhanced the function of Tregs by synergistically affecting PD-1 and TIGIT in liver transplant patients.