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Purpose: This study aimed to construct a novel platform for the detection of circulating tumor cells (CTC) in patients with hepatocellular carcinoma (HCC) and to investigate the clinical significance of epithelial cell adhesion molecule mRNA-positive (EpCAMmRNA+) CTCs using this platform.Experimental Design: An optimized platform for CTC detection was constructed by evaluating different negative enrichment, mRNA isolation, and cDNA synthesis procedures and compared with the CellSearch system. A total of 299 patients with HCC were recruited into this prospective study; of these, 157 who received curative resection, 76 who received transcatheter arterial chemoembolization (TACE), and 66 who received radiotherapy were tested using our platform. The diagnostic value of EpCAMmRNA+ CTCs was investigated in 122 patients with HCC who underwent resection and 120 control subjects.Results: The optimized negative enrichment and quantitative real-time PCR (qRT-PCR)-based CTC detection platform had high sensitivity, specificity, and reproducibility and a low sample volume requirement. This platform showed a potential diagnostic value in patients with HCC and exhibited 76.7% consistency with the CellSearch system (r = 0.54, P < 0.050). Pretreatment CTC level showed prognostic significance in patients with HCC treated with resection, TACE, and radiotherapy (all P < 0.050). Most of the patients showed a decrease in CTC levels after treatment that reflected tumor response. In contrast, patients with an increased CTC level showed disease progression after treatment.Conclusions: We established an optimized platform based on negative enrichment and qRT-PCR for highly sensitive, specific, and reproducible CTC detection. This platform might be clinically useful in auxiliary diagnosis, treatment response assessment, and early decision-making to tailor the most effective antitumor strategies. Clin Cancer Res; 20(18); 4794–805. ©2014 AACR.

Table S1, Primer pairs and probes used for quantitative real-time PCR assays; Table S2, Diagnostic performance of CTC markers in training set by logistic regression; Table S3, Performance of CTC panel and serum AFP in diagnosing various BCLC stages of HCC; Table S4, Performance of CTC panel in diagnosing HCC, stratified by AFP status; Table S5. Cox regression analyses for time to recurrence in the training and validation groups; Figure S1, Multimarker CTC screening in patients with HCC; FigureS2, The detection of stem-like phenotypes CTC subpopulations with immunofluorescent method and single-cell transcriptional analysis; Figure S3, Expression of selected CTCs in training set; Figure S4, Expression of selected CTCs in validation set; Figure S5, CTC panel positivity rates in training and validation set; Figure S6, X-tile analysis of CTC panel in training set; Figure S7, Comparison of CTC panel and EpCAM for HCC diagnosis and prognosis in training and validation sets; Figure S8, Relative expression of EMT transition markers in patients with HCC and in healthy controls

Background: In the present study, we assessed the clinical value of circulating tumor cells (CTC) with stem-like phenotypes for diagnosis, prognosis, and surveillance in hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) by an optimized qPCR-based detection platform.Methods: Differing subsets of CTCs were investigated, and a multimarker diagnostic CTC panel was constructed in a multicenter patient study with independent validation (total n = 1,006), including healthy individuals and patients with chronic hepatitis B infection (CHB), liver cirrhosis (LC), benign hepatic lesion (BHL), and HBV-related HCC, with area under the receiver operating characteristic curve (AUC-ROC) reflecting diagnostic accuracy. The role of the CTC panel in treatment response surveillance and its prognostic significance were further investigated.Results: The AUC of the CTC panel was 0.88 in the training set [sensitivity = 72.5%, specificity = 95.0%, positive predictive value (PPV) = 92.4, negative predictive value (NPV) = 77.8] and 0.93 in the validation set (sensitivity = 82.1%, specificity = 94.2%, PPV = 89.9, NPV = 89.3). This panel performed equally well in detecting early-stage and α-fetoprotein–negative HCC, as well as differentiating HCC from CHB, LC, and BHL. The CTC load was decreased significantly after tumor resection, and patients with persistently high CTC load showed a propensity of tumor recurrence after surgery. The prognostic significance of the CTC panel in predicting tumor recurrence was further confirmed [training: HR = 2.692; 95% confidence interval (CI), 1.617–4.483; P < 0.001; and validation: HR = 3.127; 95% CI, 1.360–7.190; P = 0.007].Conclusions: Our CTC panel showed high sensitivity and specificity in HCC diagnosis and could be a real-time parameter for risk prediction and treatment monitoring, enabling early decision-making to tailor effective antitumor strategies. Clin Cancer Res; 24(9); 2203–13. ©2018 AACR.

Supplementary Table S1. Sensitivity of two RNA isolation and two cDNA synthesis methods with the Hep3B cell line. Supplementary Table S2. Precision of the optimized system. Supplementary Table S3. Diagnostic value of EpCAMmRNA+ CTCs in HCC subgroups. Supplementary Table S4. Diagnostic value of the combination of EpCAMmRNA+ CTC and AFP in HCC subgroups. Supplementary Table S5. Univariate and multivariate Cox proportional regression analysis of factors associated with recurrence/progression.

Background: Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. Thyroid hormone responsive (THRSP) gene is primarily known for regulating responses to thyroid hormones, but its expression has been correlated with differential outcomes in some cancers. To date, however, its role in the progression of HCC remains unknown. Methods: The mRNA and protein expression of THRSP was measured in HCC tissues and cell lines via qPCR and western blot assays. Lentiviral transfection was used to establish stable cell lines overexpressing THRSP and shRNA was used to silence THRSP. The effects of THRSP on cell growth were then determined in vivo and in vitro. Cell migration and invasion of HCC cells were investigated using transwell and wound healing assays. Results: In tissue samples from patients, HCC tissues had decreased THRSP expression relative to adjacent healthy tissues. Further, patients with decreased THRSP protein and mRNA expression had worse outcomes. Knockdown of THRSP led to increased cell growth, migration, and invasion of HCC cells, and THRSP overexpression exerted an anti-tumor effect in vivo and in vitro. We found that increased expression of THRSP inhibited hepatocellular carcinogenesis by inhibiting the process of epithelial-to-mesenchymal transition through acting on the ERK/ZEB1 signaling pathway. Conclusion: THRSP may act as a functional tumor suppressor and was frequently reduced in HCC tissue samples. We identified a novel pathway for the THRSP/ERK/ZEB1-regulated suppression of HCC tumorigenesis and invasion. Restoring THRSP expression may represent a promising approach for HCC therapies.

Background T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells were newly identified as the subsets of cluster of CD4+ T cells. As major components of human immune system, they were found in tumor microenvironment and reported to play vital roles in the progression of cancer. But their clinical significance in Hepatocellular carcinoma (HCC) was not elucidated. Thus, this research aimed to investigate their prognostic value in HCC. Materials and methods A total of 210 subjects (including 110 HCC patients, 50 chronic hepatitis patients and 50 healthy individuals) were enrolled in the research. Tfh, Tfr cells and Treg cells from peripheral blood were measured by flow cytometry. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of Tfr-Tfh Index (TTI) in early HCC and relapse status. Its further prognostic valve was assessed by Kaplan-Meier survival estimate and log rank tests. Results Tfh cells, Tfr cells, Treg cells and TTI were all higher in HCC patients than in chronic hepatitis patients and healthy control. TTI was found to have positive correlation with the load of HBV. The AUC of TTI for early HCC and relapse status was better than other clinical indices in HBV positive patients. An optimal cutoff point for the TTI stratified the HCC patients into high (>21.96) and low index (≤21.96) groups. High TTI was significantly correlated with recurrence. Univariate and multivariate analyses revealed TTI could be a predictor for recurrence. Moreover, it retained prognostic performance for patients with lower recurrence risk. Conclusion Our research showed that TTI could be a promising indicator for early recurrence in HCC patients with HBV infection.

OBJECTIVE: To study the value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight (VLBW) infants. METHODS: A retrospective analysis was performed for 51 VLBW infants who were admitted from March 2020 to June 2021, with an age of ≤3 days and a length of hospital stay of ≥14 days. According to the diameter of patent ductus arteriosus (PDA) on days 14 and 28 after birth, the infants were divided into three groups: large PDA group (PDA diameter ≥2 mm), small PDA group (PDA diameter

Rapid progression is the major cause of the poor prognosis of hepatocellular carcinoma (HCC); however, the underlying mechanism remained unclear. Here, we found Calpain-2 (CAPN2), a well-established protease that accelerates tumor progression in several malignancies, is overexpressed in HCC and acts as an independent predictor for poor outcomes. Furthermore, CAPN2 promoted the proliferation and invasion of HCC, and showed a positive correlation with the levels of invasion-related markers. Mechanistically, a novel CAPN2-SRC positive regulatory loop was identified upstream of β-catenin to prevent its ubiquitination and degradation, and subsequently promoted HCC progression: CAPN2 could proteolyze PTP1B to form a truncation of approximately 42 kDa with increased phosphatase activity, resulting in reduced SRC Y530 phosphorylation and increased SRC kinase activity; meanwhile, CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation. Interestingly, the CAPN2-SRC loop could not only restrain most of cytoplasmic β-catenin degradation by inhibiting GSK3β pathway, but also prevented TRIM33-induced nuclear β-catenin degradation even in β-catenin-mutant cells. Present study identified a CAPN2-SRC positive loop responsible for intracellular β-catenin accumulation and signaling activation, and targeting CAPN2 protease activity might be a promising approach for preventing HCC progression.

Background and aims Intrauterine growth restriction (IUGR) is a state of slower fetal growth usually followed by a catch-up growth. Postnatal catch-up growth in IUGR models increases the incidence of pulmonary arterial hypertension in adulthood. Here, we hypothesize that the adverse pulmonary vascular consequences of IUGR may be improved by slowing down postnatal growth velocity. Meanwhile, cognitive function was also studied. Methods and results We established an IUGR rat model by restricting maternal food throughout gestation. After birth, pups were fed a regular or restricted diet during lactation by changing litter size. Thus, there were three experimental groups according to the dam/offspring diet: C/C (gold standard), IUGR with catch-up growth (R/C) and IUGR with delayed growth (R/D). In adulthood (14 weeks of age), we assessed pulmonary vascular development by hemodynamic measurement and immunohistochemistry. Our results showed that adult R/C offspring developed an elevated mean pulmonary arterial pressure (mPAP) and pulmonary arteriolar remodeling accompanied with decreased eNOS mRNA and protein expressions compared to C/C or R/D offspring. This suggested that delayed postnatal growth improved pulmonary circulation compared to postnatal catch-up growth. Conversely, adult R/D offspring performed poorly in cognition. Behavior test and electrophysiology results exhibited a reduced synaptic plasticity. Furthermore, decreased mRNA expression levels of the memory-related gene zif268 and transcription factor recruitment factor p300 in the hippocampus region were also observed in R/D group. Conclusion These findings indicate that delayed postnatal growth results in cognitive impairment, but it reverses elevations in mPAP induced by postnatal catch-up growth following IUGR.

Intrauterine life represents a window of phenotypic plasticity which carries consequences for later health in adulthood as well as health of subsequent generations. Intrauterine growth-restricted fetuses (intrauterine growth restriction [IUGR]) have a higher risk of pulmonary arterial hypertension in adulthood. Endothelial dysfunction, characterized by hyperproliferation, invasive migration, and disordered angiogenesis, is a hallmark of pulmonary arterial hypertension pathogenesis. Growing evidence suggests that intergenerational transmission of disease, including metabolic syndrome, can be induced by IUGR. Epigenetic modification of the paternal germline is implicated in this transmission. However, it is unclear whether offspring of individuals born with IUGR are also at risk of developing pulmonary arterial hypertension and endothelial dysfunction. Using a model of maternal caloric restriction to induce IUGR, we found that first and second generations of IUGR exhibited elevated pulmonary arterial pressure, myocardial, and vascular remodeling after prolonged exposure to hypoxia. Primary pulmonary vascular endothelial cells (PVECs) from both first and second generations of IUGR exhibited greater proliferation, migration, and angiogenesis. Moreover, in 2 generations, PVECs-derived ET-1 (endothelin-1) was activated by IUGR and hypoxia, and its knockdown mitigated PVECs dysregulation. Most interestingly, within ET-1 first intron, reduced DNA methylation and enhanced tri-methylation of lysine 4 on histone H3 were observed in PVECs and sperm of first generation of IUGR, with DNA demethylation in PVECs of second generation of IUGR. These results suggest that IUGR permanently altered epigenetic signatures of ET-1 from the sperm and PVECs in the first generation, which was subsequently transferred to PVECs of offspring. This mechanism would yield 2 generations with endothelial dysfunction and pulmonary arterial hypertension–like pathophysiological features in adulthood.

Objective: To identify the role of FUBP1 in hepatocellular carcinoma (HCC) progression, invasion and metastasis. Methods: The expression and clinical significance of FUBP1 in HCC was analyzed by university of California santa cruz (UCSC) Xena online bioinformatics analysis tool and TMA from 451 HCC patients who underwent surgery that removed the primary tumor. CD45-EpCam circulating tumor cell was analyzed by CellSearchTM system. Gain-of-function and loss-of-function studies for FUBP1 were performed by implementing lentivirus infection system. HCC cell proliferation, migration and long term survival were measured by CCK-8, transwell assay and clone formation test respectively. The effect of tumor cell growth in vivo was measured by using tumor xenograft mice. Results: mRNA expression level of FUBP1 is higher in HCC tumors compared to adjacent normal liver tissue. Statistical analysis shows that higher expression of FUBP1 is related with hepatitis B virus (HBV) infection background and often with microvascular invasion. Kaplan-Meier analysis revealed significantly shorter median TTR (Time to Recurrence) and overall survival (OS) in patients with high FUBP1 compared with those patients with low FUBP1. The 2-year and 5-year recurrence rate is higher, corresponding with lower OS, in patients with high FUBP1 expression than low FUBP1. Univariate and multivariate analysis revealed that FUBP expression level was an independent indicator for both TTR and OS. In addition, FUBP1 expression in tumors positively correlated with the percentage of CD45-EpCam circulating tumor cell in blood before operation. Overexpression of FUBP1 enhances HCC proliferation, invasion and metastasis. By using shRNAs to deplete FUBP1 expression, HCC cells displayed decreased cell proliferation, soft-agar growth and invasion. In contrast, FUBP1 overexpression promotes primary tumor growth and lung metastasis. qPCR and Western Blot confirmed that the FUBP1 overexpression induces upregulation of N-cadherin and Vimentin whereas inhibiting E-cadherin, important epithelial mesenchymal transition (EMT) markers. By performing gene expression profiling, we identified that FUBP1 activates the TGF-β/smad pathway through promoting the expression of THBS1 (Thrombospondin-1, TSP-1). LSKL (Peptide antagonist of Thrombospondin-1) could inhibit HCC proliferation and invasion in vitro and vivo through blocking activation of TGF-β/smad pathway mediated by THBS1. Conclusions: High level of FUBP1 in HCC predicts poor prognosis after surgery. Overexpression of FUBP1 promotes HCC proliferation, invasion and metastasis, at least partially through enriching the generation of CTCs by activates TGF-I²/smad pathway and enhancing EMT in vitro and vivo. LSKL could inhibit HCC proliferation and invasion in vitro and vivo through blocking activation of TGF-β/smad pathway mediated by THBS1. Funding: National Science and Technology Major Project (2013ZX10002011-004, 2018ZX10203204-006-002). National Key Research and Development Program (2016YFC0902400), National Natural Science Foundation of China (81572823, 81572884). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: This study was approved by the Clinical Trail Ethics Committee of Zhongshan Hospital and all other four clinical centers. Approval for research protocol and use of human subjects was obtained from the research ethics committee of Zhongshan Hospital. Informed consent was obtained from each patient.

Background The venous thromboembolism, which may be caused by increased platelet activation, is a risk factor for tumor prognosis. We determined the platelet activation status for diagnosis and predicting postoperative prognosis of hepatocellular carcinoma. Methods We conducted a prospective study of 191 patients diagnosed with HCC at Zhongshan Hospital from April 2016 to July 2016 as well as 99 healthy people. The platelet activation status was assessed by 2 platelet markers, PAC-1 and CD62p, using flow cytometry. The patients were treated with TACE or resection and monitored for ≥6 months. The diagnostic value of marker-positive platelets was determined by the receiver operating characteristic curve and the postoperative value were analyzed using the Kaplan-Meier method and COX regression model. Results All the 3 groups with high levels of marker-positive platelets were likely to be diagnosed with HCC and the PAC-1+ percentage had the best efficacy. The univariate analysis showed that the levels of PAC-1+ and CD62p+ platelets was risker factors for poor postoperative prognosis after both TACE and resection. Moreover, the multivariate analysis revealed that the level of PAC-1+ platelets was an independent risk factor for poor prognosis. Conclusions The PAC-1+ percentage of platelets is a new indicator for diagnosis and predicting postoperative prognosis.

Cyclosporine (CsA) is characterized by a narrow therapeutic window and high interindividual pharmacokinetic variability, particularly in juvenile patients. The aims of this study were to build a population pharmacokinetic model of CsA in Chinese children with hematopathy who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify covariates affecting CsA pharmacokinetics. A total of 86 Chinese children aged 8.4 ± 3.8 years (range 1.1–16.8 years) who received allo-HSCT were enrolled. Whole blood samples were collected before allo-HSCT. Genotyping was performed using an Agena MassARRAY system. A total of 1010 trough plasma concentration values of CsA and clinical data were collected. The population pharmacokinetic model of CsA was constructed using nonlinear mixed-effects modeling (NONMEM) software. The stability and performance of the final model were validated using bootstrapping and normalized prediction distribution errors. We showed that a one-compartment model with first-order elimination adequately described the pharmacokinetics of CsA. The typical values for clearance (CL) and volume of distribution (V) were 42.3 L/h and 3100 L, respectively. Body weight, postoperative days, CYP3A4*1 G genotype, estimated glomerular filtration rate and coadministration of triazole antifungal drugs were identified as significant covariates for CL. Weight and postoperative days were significant covariates for the V of CsA. Our model can be adopted to optimize the CsA dosing regimen for Chinese children with hematopathy receiving allo-HSCT.

To construct a model with the indices obtained by echocardiography to predict whether patent ductus arteriosus (PDA) was required to be treated with pharmacologic treatment or surgical ligation, we performed a prospective observational study, including all neonates with gestational age ≤ 30 weeks and assessed the hemodynamics of PDA by serial daily echocardiography examination at postnatal age of 0–12 h, 24 h, 48 h, and 72 h, respectively. The infants were classified in two groups based on whether they were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and/or surgical ligation to close the PDA from the second week after birth. We compared the echocardiographic indices between the two groups and utilized the indices to construct a model to predict which premature infants’ PDA requires intervention. The results showed that a total of forty-two preterm infants were enrolled in the study. 15 (35.7%) preterms were in the intervention group and 27 (64.3%) preterms were in the non-intervention group. Compared with the non-intervention group, the intervention group had a higher proportion of left ventricular volume overload and systemic shunt effect. In addition, the combined indicators of PDA size/weight > 3.2 mm/kg and LA/Ao > 1.4 at postnatal age of 72 h had a highest value to predict whether PDA requires intervention. These findings denoted that serial daily echocardiographic assessment can be useful in predicting whether a PDA will be closed with NSAIDs and/or surgical ligation in preterm infants with gestational age ≤ 30 weeks. Trial registration Number: IRB No. 2018-IRB-073. Date: 2018/09/21, retrospectively registered.

A boy was admitted on day 3 after birth due to shortness of breath for 2 days and cyanosis for 1 day. He had clinical manifestations of dyspnea in the early postnatal period and situs inversus, and was finally diagnosed with Kartagener syndrome. His condition was improved after oxygen therapy, anti-infective therapy, and aerosol therapy. The genetic testing showed that there was a large-fragment loss of heterozygosity, exon 48_50, and a hemizygous mutation, c.7915C > T(p.R2639X), in the DNAH5 gene. Kartagener syndrome is a rare autosomal recessive disease, and this is the first case of Kartagener syndrome diagnosed in the neonatal period in China.

OBJECTIVE: To study the clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight (ELBW) infants. METHODS: A retrospective analysis was performed for 49 ELBW infants who were admitted from January 1, 2018 to July 30, 2020, with an age of ≤14 days on admission and a duration of parenteral nutrition of > 14 days. According to the type of lipid emulsion received, the ELBW infants were divided into two groups: soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) (n=26) and medium-chain triglycerides/long-chain triglycerides (MCT/LCT) (n=23). The two groups were compared in terms of clinical features, complications, nutrition support therapy, and outcome. RESULTS: The 49 ELBW infants had a mean birth weight of (892±83) g and a mean gestational age of (28.2±2.3) weeks. There was no significant difference between the two groups in the incidence rates of hemodynamically significant patent ductus arteriosus, intraventricular hemorrhage, neonatal necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia (BPD), grade Ⅲ BPD, sepsis, and pneumonia (P > 0.05). There was also no significant difference in the duration of parenteral nutrition, the age of total enteral nutrition, and head circumference/body length/body weight at discharge between the two groups (P > 0.05). Of all the infants, 22 (45%) had parenteral nutrition-associated cholestasis (PNAC), with 13 (50%) in the SMOF group and 9 (39%) in the MCT/LCT group but there was no significant difference in the incidence of PNAC between the two groups (P > 0.05); however, the infants with PNAC in the SMOF group had significantly lower peak values of direct bilirubin and alanine aminotransferase than those in the MCT/LCT group (P < 0.05). CONCLUSIONS: The application of multi-oil fat emulsion in ELBW infants does not reduce the incidence rate of complications, but compared with MCT/LCT emulsion, SMOF can reduce the severity of PNAC in ELBW infants.

Aim: To explore the prognostic value of the pretreatment platelet (PLT) count in patients undergoing transcatheter arterial chemoembolization (TACE) with hepatocellular carcinoma (HCC). Materials & methods: We prospectively analyzed 317 hepatitis B virus-related HCC patients undergoing TACE. Time to progression (TTP) was selected to evaluate the clinical significance of PLT level in HCC patients. Results: PLT was the only parameter showing statistical significance of all the clinical characteristics between two distinct tumor response groups. After ruling out cirrhosis as a potential major confounding factor, the conclusion was further established. Higher pretreatment PLT level, portal vessel invasion and higher stratification of α-fetoprotein level were independently associated with longer TTP. The prognostic score model combining the three risk factors revealed that higher risk scores might mean shorter TTP. Conclusion: The pretreatment PLT level is a potentially useful biomarker to predict the prognostic outcomes in HCC patients undergoing TACE and deserves to be further explored in subsequent works.

OBJECTIVE: To study the clinical features of neonatal enterovirus infection, especially severe enterovirus infection. METHODS: A retrospective analysis was performed for the clinical data of 244 neonates with enterovirus infection. According to the severity of infection, they were divided into a common infection group with 231 neonates and a severe infection group with 13 neonates. Clinical features were compared between the two groups. RESULTS: Of the 244 neonates, 207 (84.8%) developed the disease in May to October, with the highest number of patients in June to July. Compared with the common infection group, the severe infection group had a significantly lower gestational age at birth and a significantly higher proportion of preterm infants (P < 0.05). Compared with the common infection group, the severe infection group had a significantly earlier onset time (P < 0.05) and significantly higher incidence rates of skin petechiae and ecchymosis, respiratory symptoms, sepsis-like manifestations (poor appetite, crying less, and less movement), concomitant diseases (such as pneumonia, myocarditis, necrotic hepatitis, and coagulation disorder), thrombocytopenia, prolonged prothrombin time, elevated creatine kinase-MB, and elevated alanine aminotransferase (P < 0.05). The severe infection group had a significantly higher mortality rate than the common infection group (P < 0.05). CONCLUSIONS: There are significant differences in onset time, common clinical manifestations, and concomitant diseases between the neonates with common and severe enterovirus infection. In the enterovirus epidemic season, if the neonates have rashes and/or sepsis-like manifestations such as poor appetite and less movement, especially if the laboratory tests suggest liver damage and coagulation dysfunction, it is necessary to pay particular attention to the possibility of severe enterovirus infection.

Novel coronavirus infection is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was named COVID-19 by the World Health Organization on January 7, 2020. In early December 2019, a number of pneumonia cases of unknown origin emerged in Wuhan, Hubei province, China. (1)(2) The disease then spread rapidly throughout China and has now become a global pandemic. As of March 23, 2020, more than 340,000 cases have been reported in more than 150 countries. Because the disease is primarily an airborne respiratory infection and is documented to have a strong human-to-human transmission, the pediatric and neonatal populations are vulnerable to this disease. However, the incidence and clinical presentations of pediatric COVID-19 infections are varied and differ from those found in adult patients. The atypical clinical presentations and 2 potential modes of transmission in neonates (ie, maternal-fetal or maternal-neonatal) have led to diagnostic and management challenges. In this perspective, we would like to share some published information from Chinese pediatric and neonatal societies about their approach to handling the 2019-2020 COVID-19 outbreak in China. Since the COVID-19 outbreak in December 2019, more than 81,000 confirmed cases have been reported in China (as of March 23, 2020). Most of these cases occurred between late January and early February 2020. The diagnosis of COVID-19 is based on the epidemiologic history of contact with an infected person, typical clinical features such as fever and respiratory distress, and a positive real-time polymerase chain reaction to the SARS-CoV-2 RNA test. The nucleic test is considered the gold standard for confirmation. As of February 8, 2020, 731 confirmed pediatric cases were reported in China, mainly from Wuhan city. (3) Relative to the total number of cases (n=34,664) reported in China, on February 8, 2020, the pediatric COVID-19 population accounted for 2.1% …

Sorafenib, a multikinase inhibitor, is a new standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, resistance to this regimen is frequently observed in clinical practice, and the molecular basis of this resistance remains largely unknown. Herein, the antitumor activity of sorafenib was assessed in 16 patient-derived xenograft (PDX) models of HCC. Gene expression analysis was conducted to identify factors that promote sorafenib resistance. Quantitative RT-PCR and immunoblotting were used to determine gene expression and activation of signaling pathways. Cell proliferation, clone formation, and transwell assays were conducted to evaluate drug-sensitivity, proliferation, and invasiveness, respectively. Kaplan-Meier analysis was used to evaluate the predictive power of biomarkers for sorafenib response. Differential gene expression analysis suggested that sorafenib resistance correlated with high karyopherin subunit alpha 3 (KPNA3) expression. Overexpression of KPNA3 in HCC cells enhanced tumor cell growth and invasiveness. Interestingly, KPNA3 was found to trigger epithelial-mesenchymal transition (EMT), a key process mediating drug resistance. On a mechanistic level, KPNA3 increased phosphorylation of AKT, which then phosphorylated ERK, and ultimately promoted TWIST expression to induce EMT and sorafenib resistance. Moreover, retrospective analysis revealed that HCC patients with low KPNA3 expression had remarkably longer survival after sorafenib treatment. Finally, we have identified a novel KPNA3-AKT-ERK-TWIST signaling cascade that promotes EMT and mediates sorafenib resistance in HCC. These findings suggest that KPNA3 is a promising biomarker for predicting patient responsiveness to sorafenib. Targeting KPNA3 may also contribute to resolving sorafenib resistance in HCC.

Background Prognosis of hepatocellular carcinoma (HCC) remains poor due to high recurrence rate and ineffective treatment options, highlighting the need to better understand the mechanism of recurrence and metastasis in HCC. Methods We first collected messenger RNA (mRNA) expression data from 442 cases of HCC patients from The Cancer Genome Atlas (TCGA) database as well as 251 HCC patients from Zhongshan Hospital during 2009 and 2010 to analyze the expression pattern from tissue microarray (TMA) of baculoviral IAP repeat containing 3 (BIRC3). Then, we used BIRC3 gain-of-function (overexpression) and loss-of-function (knockdown) studies to examine the effect of BIRC3 on HCC cell proliferation and invasion. In addition, we also investigated the undying mechanism by which BIRC3 contributes to HCC tumor progression. Functionally, we also used a BIRC3-specific inhibitor AT-406 in HCC xenograft model to explore the potential therapeutic benefit of targeting BIRC3 in liver cancer. Results BIRC3 serves as a novel prognostic indicator for HCC patients undergoing curative resection. BIRC3 promotes HCC epithelial-mesenchymal transition (EMT), cell migration, and metastasis via upregulating MAP3K7, therefore, inducing ERK1/2 phosphorylation. The specific BIRC3 inhibitor AT-406 can inhibit HCC cell proliferation and reduce pulmonary metastases. Conclusion BIRC3 induces tumor proliferation and metastasis in vitro and in vivo. BIRC3 may serve as a novel therapeutic target for liver cancer.

Annexin A3 (ANXA3) could induce progression of hepatocellular carcinoma (HCC) via promoting stem cell traits of CD133-positive cells. Moreover, serum ANXA3 showed preliminary diagnostic potential, however further validation was required. Meanwhile, the prognostic value of ANXA3 remained elusive. The present study aimed to validate diagnostic performance and further systematically investigate the prognostic value of serum ANXA3. Serum ANXA3 of 368 HCC patients was determined by enzyme-linked immunosorbent assay (ELISA); 295 of these patients underwent resection and 73 underwent transcatheter arterial chemoembolization (TACE). Diagnostic performance of ANXA3 was evaluated by receiver operating characteristic (ROC) analysis, and the prognostic value was evaluated by Cox regression and Kaplan–Meier analysis. To evaluate the relationship between serum ANXA3 and circulating CD133 mRNA-positive tumor cells (CD133mRNA+ CTCs), real-time polymerase chain reaction was conducted in 69 patients who underwent resection. Serum ANXA3 provided greater diagnostic performance than α-fetoprotein (area under the curve [AUC] 0.869 vs. 0.782), especially in early diagnosis (AUC 0.852 vs. 0.757) and discriminating HCC from patients at risk (0.832 vs. 0.736). Pretreatment ANXA3 was an independent predictor of tumor recurrence (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26–2.76, p = 0.002)/progression (HR 1.88, 95% CI 1.04–3.43, p = 0.038) and survival (resectable: HR 2.26, 95% CI 1.44–3.56, p = 0.001; unresectable: HR 2.08, 95% CI 1.10–4.05, p = 0.025), and retained its performance in low-recurrence-risk subgroups. Specifically, dynamic changes of ANXA3-positive status was associated with worse prognosis. ANXA3 was positively correlated with CD133mRNA+ CTCs (r = 0.601, p

The present study aimed to determine the levels of prothrombin induced by vitamin K absence-II (PIVKA-II) according to the Barcelona Clinic Liver Cancer (BCLC) staging system, to develop an appropriate strategy for managing hepatocellular carcinoma (HCC), particularly early HCC, and to investigate the value of PIVKA-II for predicting prognosis-associated pathological parameters. Clinical information of 117 patients with hepatitis B-associated HCC was retrospectively collected. Preoperative serum PIVKA-II and α-fetoprotein (AFP) levels were measured using a chemiluminescence method. The efficiency of PIVKA-II levels for predicting pathological parameters was evaluated using step-wise logistic regression. The receiver operator characteristic curve was used to evaluate the predictive performance of PIVKA-II levels. It was demonstrated that except for the difference between stages B and C HCC (P=0.923), serum PIVKA-II levels significantly increased according to BCLC stage (P40 mAU/ml was an independent predictor of microvascular invasion [hazard ratio (HR), 3.77; 95% confidence interval (CI), 1.31–10.88; P=0.014; and high Ki67 expression in situ (HR, 2.99; 95% CI, 1.19–7.52; P=0.020). Combined analysis of PIVKA and AFP levels may contribute to an effective strategy for the management of patients with early HCC, as high PIVKA-II levels indicated a more aggressive tumor phenotype. Further investigation of PIVKA-II levels may provide novel insights into the mechanism underlying the metastasis of HCC cells and facilitate the development of novel therapeutic strategies for HCC.

Aim: IgG4 is associated with a Th1-to-Th2 switch, which plays a vital role in metastasis, in patients with malignances; thus, we aimed to investigate its clinical significance in predicting hepatocellular carcinoma (HCC) recurrence in the present study. Methods: The correlation between serum IgG4:IgG ratio and recurrence was analyzed in a cohort of 195 patients undergoing curative resection in 2012. Another 100 patients were analyzed in a prospective independent cohort during 2012-2013 to validate the value of serum IgG4. Serum IgG4 and total IgG concentrations were measured with an automatic immune analyzer and the optimal cutoff value for serum IgG4 levels was determined by X-tile software. Results: Our data revealed that serum IgG4:IgG were significantly elevated in patients with tumor recurrence (P0.08) and low (≤0.08) groups. High serum IgG4:IgG ratio correlated with significantly shorter time-to-recurrence (median 11.85 months vs. 39.20, P=0.005). Univariate and multivariate analyses demonstrated that serum IgG4:IgG ratio is an independent indicator of tumor recurrence and this retained its clinical significance even in conventional low-recurrence-risk subgroups, including patients with low α-fetoprotein and early-stage diseases. Conclusion: Our results demonstrated that elevated serum IgG4:IgG ratio is associated with poor clinical outcomes in HCC patients and therefore, and can serve as a novel prognostic predictor for HCC patients undergoing resection. Analyzing serum IgG4 would be useful to tailor individualized therapies for patients.

Since December 2019, the outbreak of coronavirus disease (COVID-19) has become the most serious public health issue. As the special population with immature immune function, newborns with COVID-19 have been reported. Newborns with suspected or confirmed COVID-19 should be transferred to designated hospitals for isolation treatment. An emergency transfer response plan for newborns with COVID-19 has been worked out. This plan puts forward the indications for neonatal COVID-19 transfer, organization management, protection strategies for medical staff, work procedures, and disinfection methods for transfer equipment, in order to provide guidance and suggestions for the inter-hospital transfer of suspected or confirmed neonatal COVID-19.

Aim: To elucidate the integrative combinational gene regulatory network landscape of hepatocellular carcinoma (HCC) molecular carcinogenesis from diverse background. Materials & methods: Modified gene regulatory network analysis was used to prioritize differentially regulated genes and links. Integrative comparisons using bioinformatics methods were applied to identify potential critical molecules and pathways in HCC with different backgrounds. Results: E2F1 with its surrounding regulatory links were identified to play different key roles in the HCC risk factor dysregulation mechanisms. Hsa-mir-19a was identified as showed different effects in the three HCC differential regulation networks, and showed vital regulatory role in HBV-related HCC. Conclusion: We describe in detail the regulatory networks involved in HCC with different backgrounds. E2F1 may serve as a universal target for HCC treatment.

The present study aimed to determine the prognostic significance of soluble Programmed Death-ligand 1 (sPD-L1) in hepatocellular carcinoma (HCC) patients undergoing transcatheter arterial chemoembolization (TACE).We treated 114 HCC patients with TACE from 2012 to 2013 and determined their sPD-L1 levels by enzyme-linked immunosorbent assay. We evaluated prognosis according to mRESIST criteria and analyzed prognostic values by Cox regression and Kaplan-Meier analysis. We further evaluated correlations between sPD-L1 level and inflammatory status, as well as immunosuppressive environment.sPD-L1 levels were significantly increased in patients who developed HCC progression (P = 0.002) and death (P 0.001). Patients with higher pre-treatment sPD-L1 levels had a significantly shorter time to progression (10.50 vs. 18.25 months, P = 0.001) and decreased overall survival (16.50 vs. 28.50 months, P = 0.003). Importantly, sPD-L1 levels positively correlated with SII (r = 0.284, P = 0.002), sIL-2R (r = 0.239, P = 0.010), IL-10 (r = 0.283, P = 0.002), HBV-DNA loads (r = 0.229, P = 0.014), and CRP (r = 0.237, P = 0.011). Moreover, high sPD-L1 levels had increased numbers of Treg cells (FOXP3+; P = 0.026), Macrophage cells (CD68+; P = 0.014), and M2-Macrophage cells (CD163+; P = 0.026) CONCLUSIONS: sPD-L1 level is a prognostic indicator of poor outcomes after TACE. High sPD-L1 might reflect increased immune activation in an immunosuppressive environment that hindered anti-tumor response activity.

Background and Aim Myeloid-derived suppressor cells (MDSCs) play an important role in tumor progression. The aim of the present study was to investigate the prognostic value of MDSCs for early recurrence of hepatocellular carcinoma (HCC) patients undergoing curative resection. Methods MDSCs were measured by flow cytometry. The correlation between MDSCs and tumor recurrence were analyzed using a cohort of 183 patients who underwent curative resection between February 2014 and July 2015. Prognostic significance was further assessed using Kaplan-Meier survival estimates and log-rank tests. Results In vivo, CD14+HLA-DR-/low MDSCs inhibit T-cell proliferation and secretion. The frequency of CD14+HLA-DR-/low MDSCs was significantly higher in HCC patients (3.7 ± 5.3%, n = 183) than in chronic hepatitis patients (1.4 ± 0.6%, n = 25) and healthy controls (1.1 ± 0.5%, n = 50). High frequency MDSC was significantly correlated with recurrence (TTR) (P

Patients with Barcelona Clinic Liver Cancer (BCLC) 0+A are considered to have early-stage hepatocellular carcinoma (HCC). The albumin-bilirubin (ALBI) grade is a significant predictor of overall survival (OS) for HCC. However, data are lacking to support its significance for patients with early-HCC.We recruited 318 patients with early-HCC who underwent curative resection between January 2012 and August 2013. The Kaplan-Meier method and log-rank tests were used to compare OS of patients with different ALBI grades. Cox regression analysis was applied to evaluate ALBI grade as an independent predictor of OS.Early-HCC patients with ALBI grade II experienced significantly shorter OS (p0.001) and higher death rates. In the Child-Pugh (C-P) grade-A group, patients with ALBI grade I had a more favorable prognosis than those with grade II (p0.001), while the C-P grade did not distinguish patients with poor prognosis from the entire group. Cox regression analysis demonstrated that ALBI grade was the most significant independent predictor of OS, and the ALBI grade retained its clinical significance in low α-fetoprotein subgroup.ALBI grade predicted OS in patients with early-HCC. Reclassification of C-P grade according to ALBI grade might improve the management of HCC.

// Xiao-Lu Ma 1, * , Xing-Hui Gao 1, * , Zi-Jun Gong 2, * , Jiong Wu 1 , Lu Tian 1 , Chun-Yan Zhang 1 ,Yan Zhou 1 , Yun-Fan Sun 2 , Bo Hu 2 , Shuang-jian Qiu 2 , Jian Zhou 2 , Jia Fan 2 , Wei Guo 1 , Xin-Rong Yang 2 1 Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China 2 Department of Liver Surgery, Liver Cancer Institute, Zhongshan hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China * These authors have contributed equally to this work Correspondence to: Xin-Rong Yang, email: yang.xinrong@zs-hospital.sh.cn Wei Guo, email: guo.wei@zs-hospital.sh.cn Keywords: Apolipoprotein A1, hepatocellular carcinoma, serum biomarker, prognosis, circulating tumor cell Received: December 13, 2015 Accepted: September 12, 2016 Published: September 23, 2016 ABSTRACT As a major protein constituent of high density lipoprotein, Apolipoprotein A1 (ApoA-1) might be associated with cancer progression. Our study investigated the serum ApoA-1 level for the prognosis of 443 patients with hepatocellular carcinoma (HCC) and its effects on tumor cells. We found that the serum ApoA-1 level was significantly lower in HCC patients with tumor recurrence, and was an independent indicator of tumor-free survival and overall survival. Low serum ApoA-1 levels were significantly associated with multiple tumors and high Barcelona Clinic Liver Cancer stage. The circulating tumor cell (CTC) levels were significantly higher in patients with low serum ApoA-1 compared with those with high serum ApoA-1 levels (4.03 ± 0.98 vs. 1.48 ± 0.22; p =0.001). In patients with detectable CTCs, those with low ApoA-1 levels had higher recurrence rates and shorter survival times. In vitro experiments showed that ApoA-1 can inhibit tumor cell proliferation through cell cycle arrest and promote apoptosis through down regulating mitogen-activated protein kinase (MAPK) pathway. In addition, ApoA-1 might impair extracellular matrix degradation properties of tumor cells. Taken together, our findings indicate that decreased serum ApoA-1 levels are a novel prognostic factor for HCC, and the role of ApoA-1 in inhibition of proliferation and promotion of apoptosis for tumor cells during their hematogenous dissemination are presumably responsible for the poor prognosis of patients with low ApoA-1 levels. Furthermore, AopA-1 might be a promising therapeutic target to reduce recurrence and metastasis for HCC patients after resection.

e16669 Background: Cofilin1 (CFL1) is an actin-binding protein that plays an essential role in cytoskeleton regulation. However, its function in hepatocellular carcinoma (HCC) is largely unknown. The aim of study was to investigate the role of CFL1 in HCC. Methods: We used qRT-PCR and western blot assays to detect CFL1 expression. The role of CFL1 in regulating HCC cell growth and invasion were assessed by forced expression and downregulation. A tissue microarray study containing 189 HCC cases was conducted to evaluate the clinical relevance and prognostic significance of CFL1. Results: The expression level of CFL1 in high metastasis cell lines was significantly higher than that in low metastasis lines ( P < 0.05). Knockdown of CFL1 reduced the proliferation and invasion activities of Huh7 and MHHC97H cells ( P < 0.05). Western blot revealed that the cytoplasmic level of the p65 subunit of NF-κB was significantly elevated along with reduced nuclear levels and NF-κB-targeted genes MMP9, BCL2, EZH2, COX2 and VCAM1 levels significantly inhibited n HCC cells silenced for CFL1. Immunohistochemistry in a primary tissue array revealed that CFL1 expression correlated with Tumor encapsulation and microvascular invasion ( P < 0.05). High CFL1 expression patients had significantly higher recurrence and deaths rates (recurrence: 72.9% vs. 42.9%, death: 20.8% vs. 51.1%) than low CFL1 expression patients ( P < 0.001). Conclusions: CFL1 regulate the proliferation and dissemination of HCC and TNF-α induced NF-κB nuclear translocation. CFL1 may serve as a prognostic marker in HCC and might be a promising therapeutic target for suppressing metastasis.

The aim of this study was to identify novel prognostic mRNA and microRNA (miRNA) biomarkers for hepatocellular carcinoma (HCC) using methods in systems biology. Differentially expressed mRNAs, miRNAs, and long non-coding RNAs (lncRNAs) were compared between HCC tumor tissues and normal liver tissues in The Cancer Genome Atlas (TCGA) database. Subsequently, a prognosis-associated mRNA co-expression network, an mRNA-miRNA regulatory network, and an mRNA-miRNA-lncRNA regulatory network were constructed to identify prognostic biomarkers for HCC through Cox survival analysis. Seven prognosis-associated mRNA co-expression modules were obtained by analyzing these differentially expressed mRNAs. An expression module including 120 mRNAs was significantly correlated with HCC patient survival. Combined with patient survival data, several mRNAs and miRNAs, including CHST4, SLC22A8, STC2, hsa-miR-326, and hsa-miR-21 were identified from the network to predict HCC patient prognosis. Clinical significance was investigated using tissue microarray analysis of samples from 258 patients with HCC. Functional annotation of hsa-miR-326 and hsa-miR-21-5p indicated specific associations with several cancer-related pathways. The present study provides a bioinformatics method for biomarker screening, leading to the identification of an integrated mRNA-miRNA-lncRNA regulatory network and their co-expression patterns in relation to predicting HCC patient survival.

Background: With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China. Methods: All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors. Results: A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization. Conclusions: Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

A long period fiber grating (LPFG) sensor, useful for the detection of ultrasound is proposed and experimentally demonstrated. Some preliminary results are got that (indicate (the capability of the LPG sensor to successfully monitor ultrasound. The resonance wavelength of LPG is linearly related to the amplitude of the ultrasonic wave, and the frequency and duration of the ultrasonic wave hardly change the resonance wavelength. Experimental results showed that LPFG sensors could be applied to determine the corresponding parameters of ultrasonic field (by demodulating the shift of the resonant band of the LPFG.

Background: In the present study, we assessed the clinical value of circulating tumor cells (CTC) with stem-like phenotypes for diagnosis, prognosis, and surveillance in hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) by an optimized qPCR-based detection platform. Methods: Differing subsets of CTCs were investigated, and a multimarker diagnostic CTC panel was constructed in a multicenter patient study with independent validation (total n = 1,006), including healthy individuals and patients with chronic hepatitis B infection (CHB), liver cirrhosis (LC), benign hepatic lesion (BHL), and HBV-related HCC, with area under the receiver operating characteristic curve (AUC-ROC) reflecting diagnostic accuracy. The role of the CTC panel in treatment response surveillance and its prognostic significance were further investigated. Results: The AUC of the CTC panel was 0.88 in the training set [sensitivity = 72.5%, specificity = 95.0%, positive predictive value (PPV) = 92.4, negative predictive value (NPV) = 77.8] and 0.93 in the validation set (sensitivity = 82.1%, specificity = 94.2%, PPV = 89.9, NPV = 89.3). This panel performed equally well in detecting early-stage and α-fetoprotein–negative HCC, as well as differentiating HCC from CHB, LC, and BHL. The CTC load was decreased significantly after tumor resection, and patients with persistently high CTC load showed a propensity of tumor recurrence after surgery. The prognostic significance of the CTC panel in predicting tumor recurrence was further confirmed [training: HR = 2.692; 95% confidence interval (CI), 1.617–4.483; P < 0.001; and validation: HR = 3.127; 95% CI, 1.360–7.190; P = 0.007]. Conclusions: Our CTC panel showed high sensitivity and specificity in HCC diagnosis and could be a real-time parameter for risk prediction and treatment monitoring, enabling early decision-making to tailor effective antitumor strategies. Clin Cancer Res; 24(9); 2203–13. ©2018 AACR.

Background Hepatocellular carcinoma has high incidence and mortality worldwide. Liver is the site of most metabolic biotransformation, which could reflect the status of cells. Most plasma apolipoproteins, endogenous lipids and lipoproteins are synthesized in the liver. Therefore, the effects of lipid metabolites on prognosis of HCC deserved to be explored. Methods We prospectively included 58 healthy donors (HD), 50 chronic hepatitis (CH) patients and a training cohort of 189 patients with HCC who underwent curative resections at Zhongshan Hospital from January 2012 to August 2012. We identified the optimal HDLPO cutoff value at 0.98 mmol/L and used it to stratify patients into low- or high-HDLPO groups for the entire cohort and four low-recurrent-risk subgroups. We also included an independent validation group of 182 HCC patients to validate this cutoff value. Prognostic values of HDLPO and other factors were determined by Kaplan–Meier curves and the Cox proportional hazards model. Results The low-HDLPO group had a higher median tumor grade (P = 0.020) and a higher recurrence rate (P = 0.032). Results of multivariate analysis showed that preoperative γ-glutamyl transpeptidase (GGT) and HDLPO were independent predictors of recurrence. Moreover, the predictive value of HDLPO was retained in four low-recurrent-risk subgroups. As expected, clinicopathologic characteristics and predictive values were similar in the validation and training cohorts. Conclusions HDLPO is an accessible predictor of HCC recurrence after liver resections that can help identify patients who need more careful monitoring and follow-up care. Electronic supplementary material The online version of this article (doi:10.1186/s12944-017-0509-3) contains supplementary material, which is available to authorized users.