Publications by authors named "Qiang Xia"

531 Publications

Pediatric living-donor liver transplantation using right posterior segment grafts.

BMC Gastroenterol 2021 Jun 6;21(1):249. Epub 2021 Jun 6.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160 Pujian Road, Pudong New District, Shanghai, 200127, China.

Background: The right posterior segment (RPS) graft was introduced to overcome graft size discrepancy in living donor liver transplantation (LDLT). However, it was very rarely used in pediatric patients. Here we presented 4 pediatric LDLT cases receiving RPS graft between January 2015 and April 2020 in our center. A total of 1868 LDLT procedures were performed in this period.

Methods: Recipients included 1 boy and 3 girls with a median age of 45 months (range from 40 to 93 months). They were diagnosed with progressive familial intrahepatic cholestasis, propionic academia, ornithine transcarbamylase and biliary atresia, respectively. Four donors were all mothers with a median age of 32.5 years (31-38 years). Computer tomography angiography indicated posterior right branches branched off separately from main portal veins (type III variation). Three of these donor livers had 1 orifice of right hepatic veins (RHV). In the remaining 1 donor liver, the RHV showed 3 orifices and an outflow patch plastic was performed. Inferior right hepatic veins weren't found in four donor grafts. The median graft weight was 397.5 g (352-461 g) and the median graft-to-recipient weight ratio was 2.38% (1.44-2.80%).

Results: Postoperative complications occurred in neither donors nor recipients. Within the median follow-up duration of 29 months (14-64 months), four children are all alive with normal liver function.

Conclusion: In summary, for older children weighed more than 15 kg with donors' variation of type III portal veins, the use of RPS grafts could be a feasible and favorable option.
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http://dx.doi.org/10.1186/s12876-021-01835-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183075PMC
June 2021

NEIL3 prevents senescence in hepatocellular carcinoma by repairing oxidative lesions at telomeres during mitosis.

Cancer Res 2021 May 27. Epub 2021 May 27.

Department of Oncology-Pathology, Karolinska Institute

Hepatocellular carcinoma (HCC) patients suffer from few treatment options and poor survival rates. Here we report that endonuclease VIII-like protein 3 (NEIL3) is overexpressed in HCC and correlates with poor survival. All six HCC cell lines investigated were dependent on NEIL3 catalytic activity for survival and prevention of senescence, while NEIL3 was dispensable for non-transformed cells. NEIL3-depleted HCC cell lines accumulated oxidative DNA lesions specifically at telomeres, resulting in telomere dysfunctional foci and 53BP1 foci formation. Following oxidative DNA damage during mitosis, NEIL3 relocated to telomeres and recruited apurinic endonuclease 1 (APE1), indicating activation of base excision repair. META-FISH revealed that NEIL3, but not NEIL1 or NEIL2, is required to initiate APE1 and Polβ-dependent base excision repair at oxidized telomeres. Repeated exposure of NEIL3-depleted cells to oxidizing damage induced chromatin bridges and damaged telomeres. These results demonstrate a novel function for NEIL3 in repair of oxidative DNA damage at telomeres in mitosis, which is important to prevent senescence of HCC cells. Furthermore, these data suggest that NEIL3 could be a target for therapeutic intervention for HCC.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1028DOI Listing
May 2021

Antimicrobial, antioxidant and physical properties of chitosan film containing Akebia trifoliata (Thunb.) Koidz. peel extract/montmorillonite and its application.

Food Chem 2021 May 15;361:130111. Epub 2021 May 15.

Department of Food Science and Technology, 100 Wiegand Hall, Oregon State University, Corvallis, OR, USA.

A novel active packaging film was prepared in this study that incorporated Akebia trifoliata (Thunb.) Koidz. peel extracts (APE) and montmorillonite (MMT) into chitosan (CH) films. Compared with the pure CH film, the CH/APE film showed significantly higher tensile strength, elongation at break, UV light resistance, and antibacterial activity; the CH/MMT film displayed significant increases in contact angle, antioxidant activity, oxygen permeability, and thermal stability. SEM and AFM analyses showed that the additions were well-distributed into the CH matrix, but MMT induced a more compact and rougher structure. The CH-based film formula was optimized using the single-factor test and Box-Behnken design and was 0.15% MMT, 0.15% APE, and 1.50% CH. Besides, the optimized coating was applied in the postharvest preservation of A. trifoliata fruits, which yielded a significant effect on the delaying crack and mature of the fruits during 35 days of storage at 5 °C.
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http://dx.doi.org/10.1016/j.foodchem.2021.130111DOI Listing
May 2021

The metabolic hormone leptin promotes the function of T cells and supports vaccine responses.

Nat Commun 2021 05 24;12(1):3073. Epub 2021 May 24.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Follicular helper T (T) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate T function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying T regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human T differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs T generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of T cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure.
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http://dx.doi.org/10.1038/s41467-021-23220-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144586PMC
May 2021

The cGAS-STING Pathway: Novel Perspectives in Liver Diseases.

Front Immunol 2021 29;12:682736. Epub 2021 Apr 29.

The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United States.

Liver diseases represent a major global health burden accounting for approximately 2 million deaths per year worldwide. The liver functions as a primary immune organ that is largely enriched with various innate immune cells, including macrophages, dendritic cells, neutrophils, NK cells, and NKT cells. Activation of these cells orchestrates the innate immune response and initiates liver inflammation in response to the danger signal from pathogens or injured cells and tissues. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a crucial signaling cascade of the innate immune system activated by cytosol DNA. Recognizing DNA as an immune-stimulatory molecule is an evolutionarily preserved mechanism in initiating rapid innate immune responses against microbial pathogens. The cGAS is a cytosolic DNA sensor eliciting robust immunity the production of cyclic GMP-AMPs that bind and activate STING. Although the cGAS-STING pathway has been previously considered to have essential roles in innate immunity and host defense, recent advances have extended the role of the cGAS-STING pathway to liver diseases. Emerging evidence indicates that overactivation of cGAS-STING may contribute to the development of liver disorders, implying that the cGAS-STING pathway is a promising therapeutic target. Here, we review and discuss the role of the cGAS-STING DNA-sensing signaling pathway in a variety of liver diseases, including viral hepatitis, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), primary hepatocellular cancer (HCC), and hepatic ischemia-reperfusion injury (IRI), with highlights on currently available therapeutic options.
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http://dx.doi.org/10.3389/fimmu.2021.682736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117096PMC
April 2021

Aldolase A Enhances Intrahepatic Cholangiocarcinoma Proliferation and Invasion through Promoting Glycolysis.

Int J Biol Sci 2021 23;17(7):1782-1794. Epub 2021 Apr 23.

Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.

Energy metabolism reprogramming has been implicated in tumorigenesis and development. Key metabolism enzyme Aldolase A (ALDOA) has been shown to be highly expressed and involved in various kinds of cancers including hepatocellular carcinoma. In this study, we found that ALDOA was highly expressed in clinical intrahepatic cholangiocarcinoma (ICC) tissues, and its high expression was negatively correlated with overall survival (OS) and recurrence-free survival (RFS) in ICC patients. Knockdown of ALDOA expression significantly inhibited the proliferation and migration of ICC both and , while highly-expressed ALDOA in ICC cells promoted the proliferation and migration of ICC cells. By applying ALDOA inhibitor and metabolic mass spectrometry tests, we demonstrated that ALDOA modulated the biological characteristics and metabolic level of ICC cells depending on its enzymatic activity. In summary, ALDOA promotes ICC proliferation and migration by enhancing ICC cells glycolysis. Blocking enzymatic activity of ALDOA provides a strategy to inhibit ICC.
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http://dx.doi.org/10.7150/ijbs.59068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120471PMC
April 2021

CCL5-Deficiency Promotes HCC Progression by Affecting B-cell Recruitment.

J Dig Dis 2021 May 12. Epub 2021 May 12.

Department of Hepatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objectives: Abnormal expression of C-C chemokine motif ligand 5 (CCL5) occurs in many solid tumors. The mechanism by which CCL5 affects hepatocellular carcinoma (HCC) tumor progression is still unclear. Here, we aimed to evaluate the expression level of CCL5 in HCC, explore the function of CCL5 in regulating the immune microenvironment, and elaborate its regulatory mechanism involved in tumor immunity.

Methods: The relative expression level of CCL5 in the tissues of HCC patients was measured by quantitative polymerase chain reaction (qPCR) assay, and its related protein concentration was exanimated by immunohistochemistry. Serum CCL5 expression was measured by enzyme-linked immunosorbent assay (ELISA) test. C57BL/6 wild-type (WT) mice and CCL5 knockout (Ccl5 ) mice were utilized to establish the DEN-induced HCC mouse model. The population of the immune cells was determined by flow cytometry, and peripheral serum IgM level was quantified by ELISA test.

Results: CCL5 expression was low in HCC patients' tissues and peripheral blood, and its expression was correlated with the overall survival (OS), recurrence, and metastasis. In the HCC mouse model, tumor sizes of the Ccl5 group were smaller than that of the WT group. Moreover, compared to the WT group, the population size of B cells in the tumor tissues of the Ccl5 group was smaller, while there was no significant difference in the other immune cell populations. Furthermore, the IgM level in the peripheral blood of the Ccl5 group was significantly lower than that of the WT group.

Conclusions: CCL5-deficiency in HCC reduces B-cell recruitment and decreases IgM secretion, leading to rapid tumor progression. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1751-2980.12997DOI Listing
May 2021

XRCC2 repairs mitochondrial DNA damage and fuels malignant behavior in hepatocellular carcinoma.

Cancer Lett 2021 Aug 5;512:1-14. Epub 2021 May 5.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

The effects of DNA damage repair (DDR) and mitochondrial dysfunction associated with HCC have been investigated, but the functional role of mitochondrial DDR in HCC remains elusive. We studied the DDR genes and identified XRCC2 as a potential prognostic marker for HCC. XRCC2 overexpression was detected in HCC cells and shown to promote the malignant behavior of cancer cells. XRCC2 depletion in HCC cells led to DNA damage accumulation at the replication site in the nucleus. Additionally, XRCC2-depleted HCC cells exhibited impaired mitochondrial respiration and reduced complex I (CI) activity as XRCC2 was responsible for elimination of mitochondrial DNA (mtDNA) damage and maintenance of mtDNA-encoded CI-related genes' transcription in a RAD51-dependent manner. We showed that tunicamycin (Tm)-activated sXBP1 bound to the TGTCAT domain and suppressed XRCC2 expression. In HCC patients, we observed a negative correlation between XBP1 and XRCC2 expression. Moreover, XRCC2 inhibition by Tm led to genomic and mtDNA damage, which impaired the transcription of mtDNA-encoded CI-related genes and prevented tumor proliferation in vivo. We described the role of XRCC2 in mtDNA damage repair and HCC progression while unveiling the potential anti-tumor effect of Tm.
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http://dx.doi.org/10.1016/j.canlet.2021.04.026DOI Listing
August 2021

Bile Acids Impair Vaccine Response in Children With Biliary Atresia.

Front Immunol 2021 16;12:642546. Epub 2021 Apr 16.

Department of Liver Surgery and Liver Transplantation, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Vaccination is the best way to protect children under 5 years from death or disability. Children with biliary atresia (BA), which is the most common pediatric cholestatic end-stage liver disease (PELD), are more vulnerable to infectious diseases. However, the vaccination coverage and factors modulating vaccine responses in children with BA are largely unknown.

Methods: In this study, 288 children (median age: 7 months) diagnosed with BA before liver transplantation were enrolled for the evaluation of vaccination status and the factors affecting the immune response to the hepatitis B (HBV) vaccine. Moreover, 49 BA children (median age: 4 months) were enrolled for flow cytometric analysis of CD4 T cells and CD19 B cell subsets and correlations with serum bile acid levels.

Results: Generally, these children had very low routine vaccination rates for the meningococcal serogroup AC (Men AC) (41.2%), measles-mumps-rubella (MMR) (31.3%), poliomyelitis (Polio) (25.3%), hepatitis A (HAV) (25.0%), Japanese encephalitis (JE) (15.0%), diphtheria-tetanus-pertussis (DTP) (14.2%), meningococcal serogroup A (Men A) (13.5%) and varicella (VAR) (10.8%) vaccines, but not for the HBV (96.2%) and bacillus Calmette-Guérin (BCG) (84.7%) vaccines. Remarkably, 19.8% (57/288) of the patients had HBV infection. Out of 220 patients vaccinated for HBV, 113 (51.4%), 85 (38.6%) and 22 (10%) had one, two or three doses of the HBV vaccine, respectively. Furthermore, logistic regression analysis revealed that the bile acid level was an independent factor associated with poor HBV vaccine response ( = 0.03; OR = 0.394; 95% CI = 0.170-0.969). Immunophenotyping showed that bile acids were only negatively correlated with the CD19CD27IgG post-class-switched memory B cell ratio ( = 0.01).

Conclusion: This study reveals the overall vaccination rates of routine vaccines in Chinese BA children are very low and the poor HBV vaccine responses are associated with bile acids, possibly the inhibition of CD19CD27IgG post-class-switched memory B cell response.

Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR1800019165.
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http://dx.doi.org/10.3389/fimmu.2021.642546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085329PMC
April 2021

Impact of pH-dependent succinylation on the structural features and emulsifying properties of chicken liver protein.

Food Chem 2021 Oct 20;358:129868. Epub 2021 Apr 20.

Hangzhou Xueyu Biotechnology Co. Ltd., Hangzhou, Zhejiang 311201, China.

This work aims at investigating the pH-regulated relationship between the structural features and emulsifying properties of chicken liver protein (CLP) during succinylation and related mechanisms behind. The results demonstrated that the major succinylation sites occurred at lysine, histidine and tyrosine of CLP, and the succinylation degree increased by 30.66% as pH increased to 10. The succinylation pH elevation increased the solubility and oil absorption capacity of CLP, thus favoring its improvement in emulsifying properties, due to the succinylation process-induced increase in surface charge density and amphiphilic balance as well as modified network structure. However, the surface hydrophobicity of succinylated products decreased by 10.75% when the pH increased from 7 to 10. Besides, succinylation-induced variations in electrostatic repulsive and particle size distribution greatly improved the storability of the emulsions. These results suggested the great potential of pH-modulated succinylation to regulate the structure-property relationship of protein-based products.
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http://dx.doi.org/10.1016/j.foodchem.2021.129868DOI Listing
October 2021

Pooled CRISPR screening identifies mA as a positive regulator of macrophage activation.

Sci Adv 2021 Apr 28;7(18). Epub 2021 Apr 28.

Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

mA RNA modification is implicated in multiple cellular responses. However, its function in the innate immune cells is poorly understood. Here, we identified major mA "writers" as the top candidate genes regulating macrophage activation by LPS in an RNA binding protein focused CRISPR screening. We have confirmed that deficient macrophages exhibited reduced TNF-α production upon LPS stimulation in vitro. Consistently, ;Cre mice displayed increased susceptibility to bacterial infection and showed faster tumor growth. Mechanistically, the transcripts of the gene encoding a negative regulator of TLR4 signaling were highly decorated by mA modification. METTL3 deficiency led to the loss of mA modification on mRNA and slowed down its degradation, resulting in a higher level of IRAKM, which ultimately suppressed TLR signaling-mediated macrophage activation. Our findings demonstrate a previously unknown role for METTL3-mediated mA modification in innate immune responses and implicate the mA machinery as a potential cancer immunotherapy target.
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http://dx.doi.org/10.1126/sciadv.abd4742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081357PMC
April 2021

The role of tumor-associated macrophages in primary hepatocellular carcinoma and its related targeting therapy.

Int J Med Sci 2021 15;18(10):2109-2116. Epub 2021 Mar 15.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Liver macrophages consist of ontogenically distinct populations termed Kupffer cells and monocyte-derived macrophages. Tumor-associated macrophages (TAMs) inhepatocellularcarcinoma (HCC) play a prominent role in tumormicroenvironment by presenting M1(induced by IFN γ along with LPS) and M2(induced by IL-4 and IL13) polarization. Although TAMs are involved in tumor immune surveillance during the course of HCC, they contribute to tumour progression at different levels by inhibiting the anti-tumor immune response, promoting the generation of blood vessels and lymphatic vessels, and supporting the proliferation and survival of tumor cells. In this paper, the multiple functions of TAMs in HCC were reviewed to provide assistance for future researches about therapeutic approaches.
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http://dx.doi.org/10.7150/ijms.56003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040428PMC
March 2021

Research progress on hepatic machine perfusion.

Int J Med Sci 2021 3;18(9):1953-1959. Epub 2021 Mar 3.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Nowadays, liver transplantation is the most effective treatment for end-stage liver disease. However, the increasing imbalance between growing demand for liver transplantation and the shortage of donor pool restricts the development of liver transplantation. How to expand the donor pool is a significant problem to be solved clinically. Many doctors have devoted themselves to marginal grafting, which introduces livers with barely passable quality but a high risk of transplant failure into the donor pool. However, existing common methods of preserving marginal grafts lead to both high risk of postoperative complications and high mortality. The application of machine perfusion allows surgeons to make marginal livers meet the standard criteria for transplant, which shows promising prospect in preserving and repairing donor livers and improving ischemia reperfusion injury. This review summarizes the progress of recent researches on hepatic machine perfusion.
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http://dx.doi.org/10.7150/ijms.56139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040389PMC
March 2021

Ultrasound as a Promising Tool for the Green Extraction of Specialized Metabolites from Some Culinary Spices.

Molecules 2021 Mar 25;26(7). Epub 2021 Mar 25.

Faculty of Agriculture, University of Zagreb, Svetošimunska cesta 25, 10000 Zagreb, Croatia.

Spices are a popular food of plant origin, rich in various phytochemicals and recognized for their numerous properties. The aim of the study was to evaluate the antioxidant and antimicrobial activity, as well as the content of specialized metabolites, of aqueous extracts of three spice species--garlic ( L.), ginger ( L.) and turmeric ( L.)--prepared by green extraction methods. Ultrasound treatment increased the chromaticity parameter b value of turmeric and ginger extracts, thus indicating a higher yellow color predominantly due to curcuminoids characteristic of these species. Ultrasound-assisted extraction significantly increased the content of total soluble solids, phenolic compounds, total carotenoids and vitamin C. The temperature of the system was also an important factor, with the highest (70 °C) conditions in ultrasound-assisted extraction having a positive effect on thermolabile compounds (vitamin C, phenolics, total carotenoids). For example, turmeric extract treated with ultrasound at 70 °C had up to a 67% higher vitamin C content and a 69.4% higher total carotenoid content compared to samples treated conventionally at the same temperature, while ginger extracts had up to 40% higher total phenols. All different concentrations of spice extracts were not sufficient for complete inhibition of pathogenic bacterial strains of , and ; however, only garlic extracts had an effect on slowing down the growth and number of colonies. Spice extracts obtained by ultrasonic treatment contained a significantly higher level of bioactive compounds and antioxidant capacity, suggesting that the extracts obtained have significant nutritional potential and thus a significant possibility for phytotherapeutic uses.
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http://dx.doi.org/10.3390/molecules26071866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037095PMC
March 2021

Immune cell function assays in the diagnosis of infection in pediatric liver transplantation: an open-labeled, two center prospective cohort study.

Transl Pediatr 2021 Feb;10(2):333-343

Department of Liver Surgery and Liver Transplantation, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Limited studies have been performed in assessment of immune status of pediatric liver transplants (PLTs). We conducted this study to evaluate Cylex immune cell function assay in diagnosis of infection and its potential clinical application in Chinese infant PLTs.

Methods: In this prospective cohort study, 227 infant PLTs from two medical centers were enrolled, and 216 completed the study. Cylex ATP values were measured before and after liver transplantation (LT) at week 1, 2, 3, 4, 8, 12 and 24 respectively. Accordingly, patients' clinical records, including demographic data, liver function results, tacrolimus dosages and concentrations were collected and analyzed.

Results: One hundred and sixty of 216 PLTs (74.1%) were diagnosed infection based on the parameters including abnormal vital signs, imaging changes, and pathogens detection, while 44 (20.4%) were clinically stable and 12 (5.6%) experienced acute rejection. The median Cylex ATP value in infant PLTs post-surgery reduced significantly in infection group compared to stable group (median, 137 . 269 ng/mL, P<0.001). Receiver operating characteristic (ROC) curve analysis determined that the cut-off value of Cylex ATP was 152 ng/mL in diagnosis of infection [area under the curve (AUC): 0.784, 95% CI: 0.720-0.848]. Meanwhile, Cylex ATP value showed no correlation to tacrolimus dosage, blood concentration, dose-normalized concentration/dose ratio or Kaup index. However, it tended to correlate weakly with the white blood cell (WBC) number (R =0.462, P<0.0001) and lymphocyte counts (R =0.363, P<0.0001).

Conclusions: In this study, we demonstrated that low Cylex ATP represented partly over-immunosuppression and had diagnostic value in infant PLTs with infections, which might assist individualized immunosuppression in PLT patients.
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http://dx.doi.org/10.21037/tp-20-256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944184PMC
February 2021

An untargeted metabolomic insight into the high-pressure stress effect on the germination of wholegrain Oryza sativa L.

Food Res Int 2021 02 24;140:109984. Epub 2020 Dec 24.

Key Laboratory of Animal Protein Food Processing Technology of Zhejiang Province, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315832, China; State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, Zhejiang 315211, China; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau. Electronic address:

High hydrostatic pressure (HHP) technique is used as a novel abiotic stress factor for efficiently enhancing the biosynthesis of selected bioactive phytochemicals in germinated wholegrain, but the information about HHP stress-induced metabolic changes remains rather limited. Thus, the current work employed an untargeted gas chromatography-mass spectrometry-based metabolomic approach combining with multivariate models to analyze the effect of mild HHP stress (30 MPa/5 min) on the overall metabolome shifts of wholegrain brown rice (WBR) during germination. Simultaneously, major phenolics in germinated WBR (GBR) were detected by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry, to explore the potential relationship between HHP stress-induced rice metabolome alternations and the biotransformation of bioactive components. The results demonstrated that the influence of HHP stress on GBR metabolite profiles was defined by germination durations, as revealed by the differentiation of the stressed grains from the naturally germinated grains at different germination points according to principal component analysis. This was further confirmed by the results of orthogonal projections to latent structures discriminant analysis, in which the discriminating metabolites between naturally germinated and HHP-stressed grains varied across the germination process. The metabolite signatures differentiating natural and HHP-stressed germination included glycerol-3-phosphate, monosaccharides, gamma-aminobutyric acid, 2,3-butanediol, glyceryl-glycoside, amino acids and myo-inositol. Besides, HHP stress led to the increase in ribose, arabinitol, salicylic acid, azelaic acid and gamma-aminobutyric acid, as well as the reduced phenolic acids. These results demonstrated that HHP stress before germination matched with appropriate process parameters could be used as a promising technology to tailor metabolic features of germinated products, thus exerting targeted nutrition and health implications.
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http://dx.doi.org/10.1016/j.foodres.2020.109984DOI Listing
February 2021

Successful Treatment of Pediatric Refractory Burkitt Lymphoma PTLD after Liver Transplantation using Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy.

Cell Transplant 2021 Jan-Dec;30:963689721996649

Department of Hematology/Oncology, Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

In the immunocompromised setting, recipients of solid-organ or hematopoietic stem-cell transplants carry an increased risk of post-transplant lymphoproliferative disorder (PTLD). Burkitt lymphoma (BL) PTLD is a rare form of monomorphic B-cell PTLD, which lacks a standard best treatment. Here, we report the successful treatment of refractory BL-PTLD with autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. A male patient was diagnosed with BL-PTLD, with an increasing Epstein-Barr virus (EBV) viral load, at 21 months after undergoing living liver transplantation from his mother due to neonatal biliary atresia. After 10 cycles rituximab +/- intensive chemotherapy and surgical tumor resection, the tumors significantly advanced. Next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded tumor tissue, revealing one mutation in exon 5, TP53: p.A159 V, which may be associated with chemo-resistance. Thus, treatment was started with autologous anti-CD19 CAR T-cell therapy. We administered 9.0 × 10/kg autologous anti-CD19 CAR T-cells, after conditioning with cyclophosphamide and fludarabine. Unexpectedly, the patient experienced only mild (Grade II) cytokine release syndrome (CRS) without neurotoxicity. Finally, he went into complete remission (CR), and has achieved 16-month event-free survival to date. In addition, liver function has remained stably within the normal range without any immunosuppressive therapy. The literature includes only five previously reported BL cases treated with CAR T-cell therapy. In conclusion, the present case suggests that autologous anti-CD19 CAR T-cell therapy may represent a new therapeutic option for some cases of refractory BL-PTLD.Clinical trial number: ChiCTR2000032211.
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http://dx.doi.org/10.1177/0963689721996649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917414PMC
February 2021

Outcome of Liver Transplantation for Neonatal-onset Citrullinemia Type I.

Transplantation 2021 Mar;105(3):569-576

Department of Liver Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: We evaluated the outcome of liver transplantation (LT) in neonatal-onset citrullinemia type I patients, especially its impact on neurological deficits and developmental retardation.

Methods: From October 2006 to October 2019, 5 of the 2003 children who received LT at Ren Ji Hospital had been diagnosed with citrullinemia type I. The primary indication for transplantation was repeated metabolic compensation and developmental retardation in 4 patients and prophylactic transplantation in the other. Among them, 3 patients received living donor LT and 2 received orthotopic LT.

Results: All recipients had successfully recovered within the median follow-up period of 32 months (range, 6-54 mo). Transplantation restored citrulline metabolism and liver function. Plasma ammonia and citrulline concentration decreased to normal levels with no further hyperammonemic episodes being reported, even after normal diet intake began. Meanwhile, uracil-2 and orotic acid were not detected in urinary excretion. Strikingly, patients suffered developmental retardation before LT showed improved psychomotor ability and significant catch-up growth during the follow-up period. Cognitive ability, including language skills and academic performance, also greatly improved. Three patients had sustained brain injuries and exhibited severe neurological deficits before transplantation, especially repeated generalized tonic-clonic seizures. LT halted neurological deterioration and controlled seizure episodes, which further facilitated the intellectual development and improvement of life quality.

Conclusions: LT is an effective treatment for neonatal-onset citrullinemia type I patients, which reverses metabolism decompensation and improves quality of life. For patients who have suffered severe hyperammonemic insults, LT should be conducted at an early age to avoid further neurological or developmental deficits.
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http://dx.doi.org/10.1097/TP.0000000000003261DOI Listing
March 2021

Effect of remote ischemic preconditioning among donors and recipients following pediatric liver transplantation: A randomized clinical trial.

World J Gastroenterol 2021 Jan;27(4):345-357

Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Background: Studies suggested that remote ischemic preconditioning (RIPC) may effectively lessen the harmful effects of ischemia reperfusion injury during organ transplantation surgery.

Aim: To investigate the protective effects of RIPC on living liver donors and recipients following pediatric liver transplantation.

Methods: From January 2016 to January 2019 at Renji Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, 208 donors were recruited and randomly assigned to four groups: S-RIPC group (no intervention; = 55), D-RIPC group (donors received RIPC; = 51), R-RIPC group (recipients received RIPC, = 51) and DR-RIPC group (both donors and recipients received RIPC; = 51). We primarily evaluated postoperative liver function among donors and recipients and incidences of early allograft dysfunction, primary nonfunction and postoperative complications among recipients.

Results: RIPC did not significantly improve alanine transaminase and aspartate aminotransferase levels among donors and recipients or decrease the incidences of early allograft dysfunction, primary nonfunction, and postoperative complications among recipients. Limited protective effects were observed, including a lower creatinine level in the D-RIPC group than in the S-RIPC group on postoperative day 0 ( < 0.05). However, no significant improvements were found in donors who received RIPC. Furthermore, RIPC had no effects on the overall survival of recipients.

Conclusion: The protective effects of RIPC were limited for recipients who received living liver transplantation, and no significant improvement of the prognosis was observed in recipients.
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http://dx.doi.org/10.3748/wjg.v27.i4.345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852587PMC
January 2021

Determinants of anxiety and depression among pheochromocytoma patients: A case-control study.

Medicine (Baltimore) 2021 Jan;100(3):e24335

Department of Urological Surgical, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei.

Abstract: Phaeochromocytomas are catecholamine-producing neuroendocrine tumors that may manifest in many ways, specifically as sustained or paroxysmal hypertension. Data, including data from mental status screening, were prospectively collected from suspected patients. The Hospital Anxiety and Depression Scale was used as a screening tool to identify abnormal mental status. Results showed phaeochromocytoma patients were more likely to experience anxiety and depression. For future phaeochromocytoma treatment, early screening for anxiety and depression should be recommended.
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http://dx.doi.org/10.1097/MD.0000000000024335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837965PMC
January 2021

Living Donor Liver Transplantation for Patients With Hepatocellular Carcinoma: What Are the Optimal Criteria?

Liver Transpl 2021 Jun;27(6):930-931

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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http://dx.doi.org/10.1002/lt.26003DOI Listing
June 2021

Macrophage Polarization and Liver Ischemia-Reperfusion Injury.

Int J Med Sci 2021 1;18(5):1104-1113. Epub 2021 Jan 1.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Ischemia-reperfusion injury refers to organ damage caused by the previous insufficient supply of oxygen and nutrients and the involvement of metabolic by-products after blood flow is restored. Liver ischemia-reperfusion injury (IRI) has become a hot research in recent years, because it occurs in many clinical scenarios. After the introduction of liver transplantation and vascular control techniques in liver surgery, liver ischemia-reperfusion injury is considered to be an important factor affecting postoperative mortality and morbidity. As the largest immune organ in the human body, liver contain a lot of immune cells such as resident macrophages (Kupffer cells), dendritic cells, natural killer cells, and natural killer T cells which play a key role in ischemia-reperfusion injury. Among those, macrophage-mediated excessive inflammatory response is considered to be an important factor in liver ischemia-reperfusion injury. The prominent feature of liver injury is an increase in the number of macrophages in liver due to the infiltration of blood monocytes and differentiation into monocyte-derived macrophages. Liver macrophages can be divided into M1 macrophages which can promote inflammation progress and M2 macrophages that inhibit inflammation progress according to their different phenotypes and functions. Both of them can regulate liver aseptic inflammation, and play an important role in triggering, maintaining, and improving liver ischemia-reperfusion injury. This review summarizes studies of macrophage polarization on liver ischemia-reperfusion injury in recent years, to provide potential ideas for translation application in future clinical management.
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http://dx.doi.org/10.7150/ijms.52691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847630PMC
January 2021

Sleep quality and health-related quality of life in children who survived for more than 5 years after liver transplantation.

J Dig Dis 2020 Nov 10;21(11):668-670. Epub 2020 Sep 10.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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http://dx.doi.org/10.1111/1751-2980.12931DOI Listing
November 2020

Preliminary clinical experience applying donor-derived cell-free DNA to discern rejection in pediatric liver transplant recipients.

Sci Rep 2021 Jan 13;11(1):1138. Epub 2021 Jan 13.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1630 Dongfang Road, Shanghai, 200127, People's Republic of China.

Donor-derived cell-free DNA (dd-cfDNA) has been of major interest recently as a non-invasive marker of graft injury, but has not yet been extensively tested in children. From May to September in 2019, a total of 76 pediatric patients receiving a liver graft were enrolled and there were 27 patients excluded. Ultimately plasma samples and matched liver specimens from 49 patients were successfully collected whenever rejection was suspected clinically. Dd-cfDNA were analyzed and then compared to biopsy. Of these, 11 (22.4%) patients were found to have rejection by biopsy. Dd-cfDNA levels were higher among patients with rejection compared to those with no rejection. In subgroup analysis, dd-cfDNA% among patients with rejection differed from those with EBV/CMV infection and DILI patients. Similarly, observations were available concerning dd-cfDNA (cp/mL). The AUC for dd-cfDNA% and dd-cfDNA (cp/mL) were 0.878, 0.841, respectively, both of which were higher than conventional LFTs. For rejection, dd-cfDNA% ≥ 28.7% yielded a sensitivity of 72.7%, specificity 94.7% and dd-cfDNA (cp/mL) ≥ 2076 cp/mL, yielded a sensitivity of 81.8%, specificity 81.9%. Of note, the dd-cfDNA distribution was significantly different between whole liver and LLS transplantation. In the setting of pediatric LTx, dd-cfDNA appears to be a sensitive biomarker indicating the presence of rejection.International Clinical Trails Registry Platform: ChiCTR1900022406.
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http://dx.doi.org/10.1038/s41598-020-80845-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807012PMC
January 2021

High mortality associated with gram-negative bacterial bloodstream infection in liver transplant recipients undergoing immunosuppression reduction.

World J Gastroenterol 2020 Dec;26(45):7191-7203

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

Background: Immunosuppression is an important factor in the incidence of infections in transplant recipient. Few studies are available on the management of immunosuppression (IS) treatment in the liver transplant (LT) recipients complicated with infection. The aim of this study is to describe our experience in the management of IS treatment during bacterial bloodstream infection (BSI) in LT recipients and assess the effect of temporary IS withdrawal on 30 d mortality of recipients presenting with severe infection.

Aim: To assess the effect of temporary IS withdrawal on 30 d mortality of LT recipients presenting with severe infection.

Methods: A retrospective study was conducted with patients diagnosed with BSI after LT in the Department of Liver Surgery, Renji Hospital from January 1, 2016 through December 31, 2017. All recipients diagnosed with BSI after LT were included. Univariate and multivariate Cox regression analysis of risk factors for 30 d mortality was conducted in the LT recipients with Gram-negative bacterial (GNB) infection.

Results: Seventy-four episodes of BSI were identified in 70 LT recipients, including 45 episodes of Gram-positive bacterial (GPB) infections in 42 patients and 29 episodes of GNB infections in 28 patients. Overall, IS reduction (at least 50% dose reduction or cessation of one or more immunosuppressive agent) was made in 28 (41.2%) cases, specifically, in 5 (11.9%) cases with GPB infections and 23 (82.1%) cases with GNB infections. The 180 d all-cause mortality rate was 18.5% (13/70). The mortality rate in GNB group (39.3%, 11/28) was significantly higher than that in GPB group (4.8%, 2/42) ( = 0.001). All the deaths in GNB group were attributed to worsening infection secondary to IS withdrawal, but the deaths in GPB group were all due to graft-versus-host disease. GNB group was associated with significantly higher incidence of intra-abdominal infection, IS reduction, and complete IS withdrawal than GPB group ( < 0.05). Cox regression showed that rejection (adjusted hazard ratio 7.021, = 0.001) and complete IS withdrawal (adjusted hazard ratio 12.65, = 0.019) were independent risk factors for 30 d mortality in patients with GNB infections after LT.

Conclusion: IS reduction is more frequently associated with GNB infection than GPB infection in LT recipients. Complete IS withdrawal should be cautious due to increased risk of mortality in LT recipients complicated with BSI.

Is:
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http://dx.doi.org/10.3748/wjg.v26.i45.7191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723669PMC
December 2020

Characterization of the physicochemical changes and volatile compound fingerprinting during the chicken sugar-smoking process.

Poult Sci 2021 Jan 8;100(1):377-387. Epub 2020 Oct 8.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China 315211; Key Laboratory of Animal Protein Food Processing Technology of Zhejiang Province, Ningbo University, Ningbo, China 315211. Electronic address:

Sugar-smoking contributes to improving flavor attributes of meat products. However, there is rather limited information concerning the relationship between sugar-smoking process parameters and volatile compound (VC) fingerprinting as well as related quality attributes of sugar-smoked chicken. In this work, the changes in VC across the whole sugar-smoking process were determined and analyzed and physicochemical properties, free fatty acid, thiobarbituric acid reactive substances values, and E-nose were also performed to characterize the quality properties of sugar-smoked chicken breast (CB) and chicken skin (CS). Results suggested that a higher amount (P < 0.05) of total VC was observed in CS compared with CB during the whole processing, which may be correlated with higher thiobarbituric acid reactive substances values, and higher polyunsaturated fatty acid/saturated fatty acid ratio. According to E-nose analysis, the volatile flavor is clearly separated in the sugar-smoking stage. Volatile fingerprinting results revealed that heterocycles were the characteristic flavor formed during sugar-smoking process and hexanal, nonanal, furfural, 5-methyl-2-furancarboxaldehyde, and 2-acetyl-5-methylfuran were the major volatiles of the CS, which was closely related to lipid oxidation and caramelization reaction. Above all, the flavor of sugar-smoked chicken was mainly derived from CS and sugar-smoked process improved the flavor of CS. This study could provide theoretical guidance for regulation of the color and flavor of sugar-smoked chicken and further promote the development of the industry.
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http://dx.doi.org/10.1016/j.psj.2020.09.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772668PMC
January 2021

Multiple microRNAs regulate tacrolimus metabolism through CYP3A5.

Pharmacol Res 2021 Feb 18;164:105382. Epub 2020 Dec 18.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.

The CYP3A5 gene polymorphism accounts for the majority of inter-individual variability in tacrolimus pharmacokinetics. We found that the basal expression of CYP3A5 in donor grafts also played a significant role in tacrolimus metabolism under the same genetic conditions after pediatric liver transplantation. Thus, we hypothesized that some potential epigenetic factors could affect CYP3A5 expression and contributed to the variability. We used a high-throughput functional screening for miRNAs to identify miRNAs that had the most abundant expression in normal human liver and could regulate tacrolimus metabolism in HepaRG cells and HepLPCs. Four of these miRNAs (miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26-5p) were selected for testing. We found that these miRNAs inhibited tacrolimus metabolism that was dependent on CYP3A5. Putative miRNAs targeting key drug-metabolizing enzymes and transporters (DMETs) were selected using an in silico prediction algorithm. Luciferase reporter assays and functional studies showed that miR-26b-5p inhibited tacrolimus metabolism by directly regulating CYP3A5, while miR-29a-5p, miR-99a-5p, and miR-532-5p targeted HNF4α, NR1I3, and NR1I2, respectively, in turn regulating the downstream expression of CYP3A5; the corresponding target gene siRNAs markedly abolished the effects caused by miRNA inhibitors. Also, the expression of miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26b-5p in donor grafts were negatively correlated with tacrolimus C/D following pediatric liver transplantation. Taken together, our findings identify these miRNAs as novel regulators of tacrolimus metabolism.
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http://dx.doi.org/10.1016/j.phrs.2020.105382DOI Listing
February 2021

Non-metabolic role of UCK2 links EGFR-AKT pathway activation to metastasis enhancement in hepatocellular carcinoma.

Oncogenesis 2020 Dec 4;9(12):103. Epub 2020 Dec 4.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Up-regulation of Uridine-cytidine kinase 2 (UCK2), a rate-limiting enzyme of the pyrimidine salvage pathway, has been suggested in HCC, but the detailed molecular mechanisms and therapic role of UCK2 remain elusive. Bioinformatic analyses revealed that UCK2 might be a key up-regulated metabolic gene in HCCs. The expressional pattern and prognostic value of UCK2 were further examined in a large number of clinical samples. Functional assays based on site-directed mutagenesis showed that UCK2 promoted cell proliferation in a metabolic manner, but non-catalytically facilitates HCC metastasis. Mechanistically, in response to EGF, UCK2 interacted with EGFR to block EGF-induced EGFR ubiquitination and degradation, which resulted in elevated EGFR-AKT pathway activation and metastasis enhancement in HCCs. Concurrent pharmacological targeting on UCK2 and EGFR showed synergistic effects on HCC treatment. This study disclosed the non-metabolic role of UCK2 and suggested the therapeutic potential of concurrent blocking the metabolic and non-metabolic roles of UCK2 in HCC treatment.
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http://dx.doi.org/10.1038/s41389-020-00287-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718876PMC
December 2020

MELD Score Reflects the Mood, Sleep, and Daily Living Ability in Liver Transplantation Candidates: A Descriptive Study.

Ann Transplant 2020 Dec 1;25:e926857. Epub 2020 Dec 1.

Department of Psychological Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China (mainland).

BACKGROUND This study aimed to assess the psychosocial status (mood, sleep quality, and activities of daily living) of candidates on an orthotopic liver transplantation (OLT) waiting list and to identify the association between psychosocial factors and MELD score in end-stage liver disease (ESLD). MATERIAL AND METHODS Fifty-three OLT waiting list candidates completed 4 scales (Hamilton Rating Scale for Depression [HAMD-17], Hamilton Anxiety Rating Scale [HAM-A], Pittsburgh Sleep Quality Index [PSQI], Activities of Daily Living Scale [ADL]) to assess their affective status, sleep quality, and daily living ability. Candidates were divided into 2 groups, the high MELD score group (MELD score ≥15) and the low MELD score group (MELD score.
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http://dx.doi.org/10.12659/AOT.926857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720912PMC
December 2020

A single-center retrospective analysis of childhood hepatoblastoma in China.

Gland Surg 2020 Oct;9(5):1502-1512

Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: This study aimed to investigate the critical factors associated with prognosis for children with hepatoblastoma (HB) in mainland China combined with the aspect of health economics and management.

Methods: This study retrospectively reviewed children with HB in Renji Hospital Affiliated to the Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019. Descriptive analysis was used to describe the essential characteristics. Kaplan-Meier method and Cox proportional hazard models were used to estimate the survival rate and prognosis factors.

Results: For the 87 children with HB, the average survival was 2,002.8 days (95% CI: 1,798.7-2,206.9 days), the 1- and 5-year survival rates were 87.7% and 78.9%, respectively. Undergoing surgery and sex were independent prognostic factors of childhood HB. Children with HB undergoing hepatectomy (HR: 0.039) or liver transplantation (HR: 0.142) had a better prognosis, while boys were associated with a poorer prognosis (HR: 3.614). The average medical expenses for childhood HB were 40,217.5±3,862.0 CNY and liver transplantation cost more than hepatectomy.

Conclusions: The results had a comparable survival rate with other studies globally. Surgical therapy and sex are associated with the prognosis of children with HB. The economic burden of childhood HB deserves to be further explored.
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http://dx.doi.org/10.21037/gs-20-710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667112PMC
October 2020