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array:23 [ "pii" => "S1807593222000254" "issn" => "18075932" "doi" => "10.1016/j.clinsp.2022.100029" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "100029" "copyright" => "HCFMUSP" "copyrightAnyo" => "2022" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Clinics. 2022;77C:" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S180759322200028X" "issn" => "18075932" "doi" => "10.1016/j.clinsp.2022.100032" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "100032" "copyright" => "HCFMUSP" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Clinics. 2022;77C:" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original articles</span>" "titulo" => "Invariant Natural Killer T-cells and their subtypes may play a role in the pathogenesis of endometriosis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "en" ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0002" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2076 "Ancho" => 1500 "Tamanyo" => 105633 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0008" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Distribution of frequencies of iNKT cells between the endometriosis and control groups. (A) Figure shows a decrease in the total number of iNKT cells in the peripheral blood of patients with endometriosis compared to those without the disease. (B) Figure shows that the number of DN iNKT cells was decreased in the peripheral blood of patients with endometriosis compared to those without the disease.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Frederico J.S. Correa, Marina Paula Andres, Tainá Pezzin Rocha, Ana Eduarda Z. Carvalho, Thiago P.A. Aloia, Marcus V.N. Corpa, Esper G. Kallas, Cristóvão L.P. Mangueira, Edmund C. Baracat, Karina I. Carvalho, Mauricio S. Abrão" "autores" => array:11 [ 0 => array:2 [ "nombre" => "Frederico J.S." "apellidos" => "Correa" ] 1 => array:2 [ "nombre" => "Marina Paula" "apellidos" => "Andres" ] 2 => array:2 [ "nombre" => "Tainá Pezzin" "apellidos" => "Rocha" ] 3 => array:2 [ "nombre" => "Ana Eduarda Z." "apellidos" => "Carvalho" ] 4 => array:2 [ "nombre" => "Thiago P.A." "apellidos" => "Aloia" ] 5 => array:2 [ "nombre" => "Marcus V.N." "apellidos" => "Corpa" ] 6 => array:2 [ "nombre" => "Esper G." "apellidos" => "Kallas" ] 7 => array:2 [ "nombre" => "Cristóvão L.P." "apellidos" => "Mangueira" ] 8 => array:2 [ "nombre" => "Edmund C." "apellidos" => "Baracat" ] 9 => array:2 [ "nombre" => "Karina I." "apellidos" => "Carvalho" ] 10 => array:2 [ "nombre" => "Mauricio S." "apellidos" => "Abrão" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Highlights" "clase" => "author-highlights" "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara019" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">•</span><p id="para0001" class="elsevierStylePara elsevierViewall">The frequency of iNKT cells in general and their subtype double-negative are related to endometriosis.</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">•</span><p id="para0002" class="elsevierStylePara elsevierViewall">The expression of IL-17 and CCR7 by iNKT cells are related to endometriosis-associated pain symptoms.</p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">•</span><p id="para0003" class="elsevierStylePara elsevierViewall">iNKT cells are numerically and functionally altered in women with endometriosis.</p></li></ul></p></span>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S180759322200028X?idApp=UINPBA00004N" "url" => "/18075932/000000770000000C/v3_202308251443/S180759322200028X/v3_202308251443/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S1807593222000370" "issn" => "18075932" "doi" => "10.1016/j.clinsp.2022.100041" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "100041" "copyright" => "HCFMUSP" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Clinics. 2022;77C:" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original articles</span>" "titulo" => "Changes in postural balance associated with a woman's aging process" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "en" ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0001" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3050 "Ancho" => 2083 "Tamanyo" => 316809 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Comparison of postural balance with eyes open between age groups. (A) Latero-lateral COP displacement; (B) Antero-posterior COP displacement; (C) Mean velocity calculated from the total displacement of the COP in all directions; (D) Range: sum of the maximum and minimum displacement of the COP in latero-lateral direction; (E) Range: sum of the maximum and minimum displacement of the COP in anteroposterior direction; (F) Area of 95% from an ellipse of the total COP displacement. * p-value ≤0.05 ANOVA with Bonferroni Correction (Pos hoc).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Guilherme Carlos Brech, Tatiana Godoy Bobbio, Kelem de Negreiros Cabral, Patrícia Mota Coutinho, Leila Regina de Castro, Luis Mochizuki, Jose Maria Soares-Junior, Edmund Chada Baracat, Luiz Eugênio Garcez Leme, Julia Maria D'Andréa Greve, Angélica Castilho Alonso" "autores" => array:11 [ 0 => array:2 [ "nombre" => "Guilherme Carlos" "apellidos" => "Brech" ] 1 => array:2 [ "nombre" => "Tatiana Godoy" "apellidos" => "Bobbio" ] 2 => array:2 [ "nombre" => "Kelem de Negreiros" "apellidos" => "Cabral" ] 3 => array:2 [ "nombre" => "Patrícia Mota" "apellidos" => "Coutinho" ] 4 => array:2 [ "nombre" => "Leila Regina de" "apellidos" => "Castro" ] 5 => array:2 [ "nombre" => "Luis" "apellidos" => "Mochizuki" ] 6 => array:2 [ "nombre" => "Jose Maria" "apellidos" => "Soares-Junior" ] 7 => array:2 [ "nombre" => "Edmund Chada" "apellidos" => "Baracat" ] 8 => array:2 [ "nombre" => "Luiz Eugênio Garcez" "apellidos" => "Leme" ] 9 => array:2 [ "nombre" => "Julia Maria D'Andréa" "apellidos" => "Greve" ] 10 => array:2 [ "nombre" => "Angélica Castilho" "apellidos" => "Alonso" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Highlights" "clase" => "author-highlights" "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara007" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">•</span><p id="para0001" class="elsevierStylePara elsevierViewall">Aging process increases postural oscillations, worsening the postural balance.</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">•</span><p id="para0002" class="elsevierStylePara elsevierViewall">Poor postural balance is more evident in the elderly over 80-years old.</p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">•</span><p id="para0003" class="elsevierStylePara elsevierViewall">Deterioration of the postural control systems and the increased risk of falls.</p></li><li class="elsevierStyleListItem" id="celistitem0004"><span class="elsevierStyleLabel">•</span><p id="para0004" class="elsevierStylePara elsevierViewall">Important identify factors related to falls and postural balance.</p></li></ul></p></span>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222000370?idApp=UINPBA00004N" "url" => "/18075932/000000770000000C/v3_202308251443/S1807593222000370/v3_202308251443/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original articles</span>" "titulo" => "CLEC14A was up-regulated in hepatocellular carcinoma and may function as a potential diagnostic biomarker" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Lang Yan, Xiang Li, Yunfeng Yuan" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Lang" "apellidos" => "Yan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn1" ] ] ] 1 => array:3 [ "nombre" => "Xiang" "apellidos" => "Li" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn1" ] ] ] 2 => array:4 [ "nombre" => "Yunfeng" "apellidos" => "Yuan" "email" => array:1 [ 0 => "yyf666180@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0001" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Chongqing University Three Gorges Hospital, Chongqing, China" "identificador" => "aff0001" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0001" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0002" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1320 "Ancho" => 2667 "Tamanyo" => 135504 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">CLEC14A may function as a potential diagnostic biomarker. (A) Results of ROC analysis for tissue expression of CLEC14A. (B) Results of ROC analysis for PBMCs expression of CLEC14A.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Introduction</span><p id="para0010" class="elsevierStylePara elsevierViewall">Hepatocellular Carcinoma (HCC) is a common malignancy of the liver system <a class="elsevierStyleCrossRefs" href="#bib0001">[1–3]</a>. Nowadays, because of the changes in the climate, lifestyle as well as structure of the diet, the incidence rate of HCC is increasing every year <a class="elsevierStyleCrossRefs" href="#bib0004">[4–6]</a>. The early stage of HCC did not have special symptoms; therefore, most of the HCC patients reached the advanced stage when HCC was first diagnosed. This always leads to the poor survival rate of the disease <a class="elsevierStyleCrossRefs" href="#bib0007">[7–9]</a>. Thus, to further explore the possible underlying mechanism of the genesis of HCC and find reliable biomarker is of great importance for the diagnosis and treatment of HCC.</p><p id="para0011" class="elsevierStylePara elsevierViewall">In recent years, great efforts have been made to identify biomarkers for the early diagnosis of HCC. For example, Luo et al. identified and verified several new serum metabolite biomarkers which have shown good diagnostic value for HCC <a class="elsevierStyleCrossRef" href="#bib0010">[10]</a>. Moreover, by using mass spectrometry technology, Li et al. found that inter-alpha-trypsin inhibitor heavy chain four may be used for the early diagnosis of HCC <a class="elsevierStyleCrossRef" href="#bib0011">[11]</a>. Furthermore, Qin et al. suggested that the serum expression of ST8SIA6-AS1 may be a potential diagnostic biomarker for HCC <a class="elsevierStyleCrossRef" href="#bib0012">[12]</a>.</p><p id="para0012" class="elsevierStylePara elsevierViewall">The C-type Lectin-like receptors (CLECs) family consist of different transmembrane pattern recognition receptors <a class="elsevierStyleCrossRefs" href="#bib0013">[13–15]</a>. Previous studies suggested that CLECs play key roles in different biological events. For example, regulating the growth of cancer cells, maintaining body hemostasis, facilitating cell communication, etc <a class="elsevierStyleCrossRefs" href="#bib0016">[16–18]</a>. CLEC14A is a newly discovered CLEC protein, and reports on the roles of CLEC14A in different diseases were rate. Studies on CLEC14A were mainly focused on the regulator roles of CLEC14A in immune cells and angiogenesis <a class="elsevierStyleCrossRefs" href="#bib0019">[19–21]</a>.</p><p id="para0013" class="elsevierStylePara elsevierViewall">The roles of CLEC14A in some types of cancers, for example, renal clear cell carcinoma <a class="elsevierStyleCrossRef" href="#bib0022">[22]</a> lung adenocarcinoma <a class="elsevierStyleCrossRef" href="#bib0023">[23]</a>, uterine carcinosarcoma <a class="elsevierStyleCrossRef" href="#bib0024">[24]</a>, have been discussed previously. However, up to now, the potential roles of CLEC14A in hepatocellular carcinoma still need to be explored. Therefore, the authors designed the present study to investigate the potential clinical value of CLEC14A in hepatocellular carcinoma.</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Materials and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Sample collection and clinical information</span><p id="para0014" class="elsevierStylePara elsevierViewall">In the present study, the authors enrolled a total of 105 patients with HCC. Patients were all pathological diagnosed with HCC by biopsy at Chongqing University Three Gorges Hospital. None of the patients received anti-tumor therapies before diagnosis. The HCC tumor samples, as well as the adjacent non-tumorous normal tissues (3‒5 cm from the tumor samples) of 105 patients were collected during the surgery process. The PBMCs of the patients and healthy controls were also collected. All tissue and serum samples were stored at -80°C until needed. The content of the current work has been approved by the ethical committee of Chongqing University Three Gorges Hospital (n° 500032175), and each patient signed the informed consent.</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Real-time quantitative polymerase chain reaction (RT-qPCR)</span><p id="para0015" class="elsevierStylePara elsevierViewall">RNA of the liver tissues, PBMCs, and cells was extracted by TRIzol® reagent (Invitrogen; Thermo Fisher Scientific, Inc.). Reverse transcription and qPCR were carried out using One Step SuperRT-PCR Mix Kit (T2240; Solarbio) on Mastercycler® nexus (6330000072; Eppendorf, Inc.). All primers used in the present study were designed and synthesized by Genewiz Inc. GAPDH was used as the internal reference gene. The thermocycling conditions were as follows: denaturation at 94°C for 60s, then annealing at 37°C for 60s for 30 cycles. At last, the extension was at 72°C for 120s. The 2<span class="elsevierStyleSup">ΔΔCt</span> method was used for calculating the fold change in gene expression level. The sequences of the primers were: CLEC14A forward primer, 5’-CTGCACCACGCTACCATGAA-3’; CLEC14A reverse primer, 5’-CCAGGAGAAACCCCGCAAA-3’; GAPDH forward primer, 5’-TGTGGGCATCAATGGATTTGG-3’; GAPDH reverse primer, 5’- ACACCATGTATTCCGGGTCAAT-3’.</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Cell culture</span><p id="para0016" class="elsevierStylePara elsevierViewall">Human normal liver cell line L02 cells, as well as HCC cell lines, including HuH-7 and SK-HEP-1 were purchased from the Cell Bank of China (Shanghai, China). The cells were maintained by PRMI-1640 medium containing 10% FBS as well as penicillin-streptomycin (Beyotime, Shanghai, China).</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Transfection</span><p id="para0017" class="elsevierStylePara elsevierViewall">CLEC14A siRNA was obtained from Genepharma (Shanghai, China). To knock down CLEC14A expression in HuH-7 cells, the cells were transfected with 50 nM CLEC14A siRNA using Lipofectamine 3000 (Invitrogen) based on the protocols provided by the manufacturer.</p></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Cell viability assay</span><p id="para0018" class="elsevierStylePara elsevierViewall">To determine the effects of CLEC14A on the viability of HCC cells, CCK-8 proliferation analysis was performed. Briefly, HuH-7 cells have been seeded onto 96-well plates (1 × 10<span class="elsevierStyleSup">4</span> cells/well) and transfected with or without CLEC14A siRNA. To detect the cell viability, each well was treated by CCK-8 reagent at a different time point, and the OD value at 450 nm was recorded by a microplate reader.</p></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">Cell apoptosis assay</span><p id="para0019" class="elsevierStylePara elsevierViewall">Annexin V/PI cell apoptosis kit was used to determine the effects of CLEC14A on the apoptosis of HuH-7 cells. Briefly, cells were maintained in a 6-well plate and treated with Annexin V and PI according to the instructions provided by the manufacturer. The apoptosis of the cells in each sample has been determined using a flow cytometer (FACSCalibur Flow Cytometer, BD, CA, USA).</p></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">Statistical analysis</span><p id="para0020" class="elsevierStylePara elsevierViewall">Statistical analysis has been carried out by SPSS 23.0 (Chicago, IL, USA). Data were shown as a mean ± SD. Comparison between two groups was analyzed by student <span class="elsevierStyleItalic">t</span>-test. Receiver Operating Characteristic (ROC) was used for evaluating the potential diagnostic value of CLEC14A. If the p-value is less than 0.05, the authors considered the comparison between the two groups were significantly different.</p></span></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Results</span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Over-expression of CLEC14A was in HCC</span><p id="para0021" class="elsevierStylePara elsevierViewall">Firstly, the expression of CLEC14A in HCC tumor tissue, as well as non-tumorous adjacent tissues, was examined and compared. The clinical information of the patients is shown in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>. Increased expression of CLEC14A was correlated with tumor size (<span class="elsevierStyleItalic">p</span> = 0.0423) and differentiation (<span class="elsevierStyleItalic">p</span> = 0.0255). The authors found that CLEC14A mRNA expression was dramatically increased in HCC tumor tissues in comparison with the adjacent non-tumorous tissues (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>A, <span class="elsevierStyleItalic">p</span> < 0.01). Moreover, CLEC14A mRNA expression was also significantly increased in PBMCs of HCC patients (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>B, <span class="elsevierStyleItalic">p</span> < 0.01), and the levels of CLEC14A in HCC tumors and PBMCs were positively correlated (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>C; <span class="elsevierStyleItalic">r</span> = 0.3502, <span class="elsevierStyleItalic">p</span> = 0.0002).</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><elsevierMultimedia ident="fig0001"></elsevierMultimedia></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">CLEC14A may function as a potential diagnostic biomarker for HCC</span><p id="para0022" class="elsevierStylePara elsevierViewall">Next, the potential diagnostic value of CLEC14A for HCC was determined by ROC analysis. The authors found that the AUC value of CLEC14A expression in tissue samples for the diagnosis of HCC was 0.8571 (<a class="elsevierStyleCrossRef" href="#fig0002">Fig. 2</a>A, 95% CI = 0.8032 to 0.9109), and for CLEC14A expression in PBMCs for the diagnosis of HCC was 0.8145 (<a class="elsevierStyleCrossRef" href="#fig0002">Fig. 2</a>B, 95% CI = 0.7542 to 0.8748).</p><elsevierMultimedia ident="fig0002"></elsevierMultimedia></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Over-expression of CLEC14A was in HCC cells</span><p id="para0023" class="elsevierStylePara elsevierViewall">Furthermore, expressions of CLEC14A in human normal liver cell line L02 cells, HCC cell lines HuH-7 and SK-HEP-1 were examined and compared. The authors found that the expression of CLEC14A was significantly increased in both HuH-7 and SK-HEP-1 cells in comparison with L02 cells (<a class="elsevierStyleCrossRef" href="#fig0003">Fig. 3</a>, <span class="elsevierStyleItalic">p</span> < 0.01). Because HuH-7 has shown a higher CLEC14A level than SK-HEP-1, it has been used for further analysis.</p><elsevierMultimedia ident="fig0003"></elsevierMultimedia></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0021">Knockdown of CLEC14A decreased the viability and increased the apoptosis of HuH-7 cell</span><p id="para0024" class="elsevierStylePara elsevierViewall">Finally, to further investigate the roles of CLEC14A in the pathogenesis of HCC, the authors cultured HuH-7 cells with CLEC14A siRNA, and the effects of CLEC14A on the cell growth as well as apoptosis was determined by MTT and flow cytometry methods. Results of the MTT assay indicated that CLEC14A siRNA-transfected cells had shown decreased cell viability on 24h, 48h, and 72h (<a class="elsevierStyleCrossRef" href="#fig0004">Fig. 4</a>A). Moreover, down-regulation of CLEC14A also significantly promoted the apoptosis of HuH-7 cells <span class="elsevierStyleItalic">in vitro</span> (<a class="elsevierStyleCrossRef" href="#fig0004">Fig. 4</a>B, <span class="elsevierStyleItalic">p</span> < 0.01).</p><elsevierMultimedia ident="fig0004"></elsevierMultimedia></span></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0022">Discussion</span><p id="para0025" class="elsevierStylePara elsevierViewall">In the present study, the authors have explored the roles of CLEC14A in HCC. The present study's results proved that CLEC14A may function as an oncogene in HCC, and CLEC14A may exert its carcinogenic effects via increasing the viability and decreasing the apoptosis of HCC cells.</p><p id="para0026" class="elsevierStylePara elsevierViewall">In recent years, CLEC family proteins were found to be up-regulated in several cancers, and the roles of CLEC14A as onco-genes have been investigated in different works [<a class="elsevierStyleCrossRef" href="#bib0020">20</a>,<a class="elsevierStyleCrossRef" href="#bib0024">24</a>,<a class="elsevierStyleCrossRef" href="#bib0025">25</a>], However, little was known about the function of CLEC14A in HCC. In the present study, the authors have observed that CLEC14A was significantly up-regulated in HCC tumors on both mRNA and protein levels; moreover, results of the clinical analysis showed the levels of CLEC14A in HCC patients were positively correlated with tumor size and differentiation. Interestingly, the results of ROC analysis (AUC 0.8571 for tissue and 0.8145 for PBMCs) indicated that the expression of CLEC14A can distinguish the tumor tissue and the non-tumor adjacent tissue. In a previous study, it has been reported that the AUC of Alpha-Fetoprotein (AFP), which is a currently used cancer biomarker for HCC, is 0.646, and for ITIH4, it is 0.667 <a class="elsevierStyleCrossRef" href="#bib0011">[11]</a>. Therefore, CLEC14A has shown better diagnostic value than the above biomarkers for the diagnosis of HCC. Taken together, the present study's data suggested that CLEC14A may function as an oncogene in HCC, and the levels of CLEC14A were positively correlated with the severity and progression of HCC.</p><p id="para0027" class="elsevierStylePara elsevierViewall">The CLEC family proteins have been known to play critical roles in the proliferation and apoptosis of cancer cells [<a class="elsevierStyleCrossRef" href="#bib0021">21</a>,<a class="elsevierStyleCrossRef" href="#bib0026">26</a>,<a class="elsevierStyleCrossRef" href="#bib0027">27</a>]. To further investigate the roles of CLEC14A in the pathogenesis of HCC, the authors cultured HCC cells with CLEC14A siRNA, and the effects of CLEC14A on the viability and apoptosis of HuH-7 cells were examined. The authors observed that CLEC14A siRNA-transfected cells had shown decreased cell viability as well as increased apoptosis, suggesting that CLEC14A can regulate the growth and apoptosis of HCC cells <span class="elsevierStyleItalic">in vitro</span>.</p><p id="para0028" class="elsevierStylePara elsevierViewall">The present study has several limitations. The authors only performed clinical analysis and cell studies, and in the future, the roles of CLEC14A in HCC should also be further explored using animal models. Also, current work was based on the Asian population, and the roles of CLEC14A in other races should also be evaluated.</p><p id="para0029" class="elsevierStylePara elsevierViewall">In conclusion, the authors proved that CLEC14A was up-regulated in HCC, and CLEC14A can regulate the growth as well as apoptosis of HCC cells in vitro. The present data have provided novel evidence for the treatment of HCC.</p><span id="sec0016" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0023">Authors' contributions</span><p id="para0030" class="elsevierStylePara elsevierViewall">Lang Yan was responsible for the organization and coordination of the trial. Xiang Li was the chief investigator and was responsible for the data analysis. Lang Yan, Xiang Li, and Yunfeng Yuan developed the trial design. All authors contributed to the writing of the final manuscript.</p></span></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1954057" "titulo" => "Highlights" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abss0001" ] ] ] 1 => array:3 [ "identificador" => "xres1954056" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0003" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abss0004" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abss0005" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0006" "titulo" => "Conclusions" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1682130" "titulo" => "Keywords" ] 3 => array:2 [ "identificador" => "sec0001" "titulo" => "Introduction" ] 4 => array:3 [ "identificador" => "sec0002" "titulo" => "Materials and methods" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0003" "titulo" => "Sample collection and clinical information" ] 1 => array:2 [ "identificador" => "sec0004" "titulo" => "Real-time quantitative polymerase chain reaction (RT-qPCR)" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Cell culture" ] 3 => array:2 [ "identificador" => "sec0006" "titulo" => "Transfection" ] 4 => array:2 [ "identificador" => "sec0007" "titulo" => "Cell viability assay" ] 5 => array:2 [ "identificador" => "sec0008" "titulo" => "Cell apoptosis assay" ] 6 => array:2 [ "identificador" => "sec0009" "titulo" => "Statistical analysis" ] ] ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0011" "titulo" => "Over-expression of CLEC14A was in HCC" ] 1 => array:2 [ "identificador" => "sec0012" "titulo" => "CLEC14A may function as a potential diagnostic biomarker for HCC" ] 2 => array:2 [ "identificador" => "sec0013" "titulo" => "Over-expression of CLEC14A was in HCC cells" ] 3 => array:2 [ "identificador" => "sec0014" "titulo" => "Knockdown of CLEC14A decreased the viability and increased the apoptosis of HuH-7 cell" ] ] ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Discussion" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0016" "titulo" => "Authors' contributions" ] ] ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-07-05" "fechaAceptado" => "2021-11-09" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1682130" "palabras" => array:4 [ 0 => "CLEC14A" 1 => "Hepatocellular carcinoma" 2 => "ROC" 3 => "Diagnosis" ] ] ] ] "tieneResumen" => true "highlights" => array:2 [ "titulo" => "Highlights" "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara007" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">•</span><p id="para0002" class="elsevierStylePara elsevierViewall">Over-expression of CLEC14A was in HCC.</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">•</span><p id="para0003" class="elsevierStylePara elsevierViewall">CLEC14A may function as a potential diagnostic biomarker for HCC.</p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">•</span><p id="para0004" class="elsevierStylePara elsevierViewall">Over-expression of CLEC14A was in HCC cells.</p></li><li class="elsevierStyleListItem" id="celistitem0004"><span class="elsevierStyleLabel">•</span><p id="para0005" class="elsevierStylePara elsevierViewall">Knockdown of CLEC14A decreased the viability and increased the apoptosis of HuH-7 cell.</p></li></ul></p></span>" ] "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Objective</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">The current work aimed to investigate the expression and potential clinical significance of C-type Lectin domain family 14 (CLEC14A) in hepatocellular carcinoma.</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Methods</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">The relative expressions of CLEC14A in the Hepatocellular Carcinoma (HCC) tissue and adjacent normal tissue of 105 HCC patients were examined using RT-qPCR methods. Furthermore, Receiver Operating Characteristic (ROC) curve was drawn for exploring the diagnostic value of CLEC14A. Next, the expressions of CLEC14A in HCC cell lines and normal liver epithelial cells were compared, and the effects of knockdown of CLEC14A on the growth and apoptosis of HCC cells were examined.</p></span> <span id="abss0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Results</span><p id="spara010" class="elsevierStyleSimplePara elsevierViewall">The authors found that the expression of CLEC14A was markedly increased in hepatocellular carcinoma tumors in comparison with the adjacent tissue, and the expression level of CLEC14A was positively correlated with the size and differentiation of the tumor. Moreover, results of ROC analysis showed CLEC14A might function as a sensitive diagnostic biomarker for HCC. Furthermore, CLEC14A was up-regulated in HCC cell lines, and transient over-expression of CLEC14A decreased the proliferation and increased the apoptosis of HCC cells <span class="elsevierStyleItalic">in vitro</span>.</p></span> <span id="abss0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0006">Conclusions</span><p id="spara011" class="elsevierStyleSimplePara elsevierViewall">Our results suggested that CLEC14A was up-regulated in HCC and might function as a potential diagnostic marker.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0003" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abss0004" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abss0005" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0006" "titulo" => "Conclusions" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="notep0001">Contribute equally to this work.</p>" "identificador" => "fn1" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0001" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2061 "Ancho" => 2333 "Tamanyo" => 210578 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Up-regulation of CLEC14A in HCC. (A) Comparison between the expression of CLEC14A in HCC tumor and normal adjacent tissues. (B) Comparison between the expression of CLEC14A in PBMCs of HCC patients and healthy controls. (C) Results of correlation analysis. *** <span class="elsevierStyleItalic">p</span> < 0.01.</p>" ] ] 1 => array:8 [ "identificador" => "fig0002" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1320 "Ancho" => 2667 "Tamanyo" => 135504 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">CLEC14A may function as a potential diagnostic biomarker. (A) Results of ROC analysis for tissue expression of CLEC14A. (B) Results of ROC analysis for PBMCs expression of CLEC14A.</p>" ] ] 2 => array:8 [ "identificador" => "fig0003" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1276 "Ancho" => 1542 "Tamanyo" => 63767 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0004" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Up-regulation of CLEC14A in HCC cells. *** <span class="elsevierStyleItalic">p</span> < 0.01.</p>" ] ] 3 => array:8 [ "identificador" => "fig0004" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2466 "Ancho" => 1542 "Tamanyo" => 215768 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Effect of CLEC14A on the growth and apoptosis of HCC cells <span class="elsevierStyleItalic">in vitro</span>. (A) Effect of CLEC14A on the viability of HCC cells in vitro (** <span class="elsevierStyleItalic">p</span> < 0.01). (B) Effect of CLEC14A on the apoptosis of HCC cells in vitro (** <span class="elsevierStyleItalic">p</span> < 0.01).</p>" ] ] 4 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">*<span class="elsevierStyleItalic">p</span> < 0.05.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">CLEC14A low group (<span class="elsevierStyleItalic">n</span> = 51) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">CLEC14A high group (<span class="elsevierStyleItalic">n</span> = 54) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0005"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Age \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0006"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0007"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.6865 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0009"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">≥ 60 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">< 60 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0017"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Sex \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.8049 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0029"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Tumor size \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><span class="elsevierStyleBold">0.0423<span class="elsevierStyleSup">a</span></span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0033"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">< 5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0037"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">≥ 5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0041"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">TNM stage \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.1989 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0045"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">I-II \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0049"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">III-IV \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0053"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Tumor nodules \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.6962 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0057"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">44 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">≥ 2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0065"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.5237 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0069"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0073"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0077"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Differentiation \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><span class="elsevierStyleBold">0.0255<span class="elsevierStyleSup">a</span></span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0081"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Well-moderate \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0085"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Poor \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0089"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Metastasis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0985 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0093"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0097"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0099"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3252714.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Clinicopathological characteristics of the patients.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:27 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "LI-RADS treatment response algorithm for detecting incomplete necrosis in hepatocellular carcinoma after locoregional treatment: a systematic review and meta-analysis using individual patient data" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "TH Kim" 1 => "S Woo" 2 => "I Joo" 3 => "MR Bashir" 4 => "MS Park" 5 => "LMB Burke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00261-021-03122-8" "Revista" => array:7 [ "tituloSerie" => "Abdom Radiol (NY)" "fecha" => "2021" "volumen" => "46" "numero" => "8" "paginaInicial" => "3717" "paginaFinal" => "3728" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34027566" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0002" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of m6A methyltransferase-related lncRNA signature for predicting immunotherapy and prognosis in patients with hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L Li" 1 => "R Xie" 2 => "G. Lu" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Biosci Rep" "fecha" => "2021" "volumen" => "41" "numero" => "6" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0003" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Wiercinska-Drapalo A. Change in ɣ-glutamyl transpeptidase activity as a useful tool in identifying a group of patients with elevated risk of hepatocellular carcinoma development after DAA treatment of chronic hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D Orzechowska" 1 => "K Klimowicz" 2 => "A Stepien" 3 => "T Mikula" 4 => "M Sapula" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5114/ceh.2021.104466" "Revista" => array:7 [ "tituloSerie" => "Clin Exp Hepatol" "fecha" => "2021" "volumen" => "7" "numero" => "1" "paginaInicial" => "93" "paginaFinal" => "100" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34027121" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0004" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical aspects and treatment of hepatocellular carcinoma in north-eastern Poland" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "TW Lapinski" 1 => "A Tarasik" 2 => "M Januszkiewicz" 3 => "R. Flisiak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5114/ceh.2021.104631" "Revista" => array:7 [ "tituloSerie" => "Clin Exp Hepatol" "fecha" => "2021" "volumen" => "7" "numero" => "1" "paginaInicial" => "79" "paginaFinal" => "84" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34027119" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0005" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Galectin-3 is not useful for hepatocellular carcinoma surveillance in cirrhotic patients, but it may be a marker of cirrhosis development" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "ES Nassar" 1 => "YA Elkalbashawy" 2 => "A Kamal" 3 => "NHE. Zakaria" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Exp Hepatol" "fecha" => "2021" "volumen" => "7" "numero" => "1" "paginaInicial" => "74" "paginaFinal" => "78" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0006" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatocellular carcinoma recurrence after directly acting antivirals for chronic hepatitis C: a 2-year follow-up study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A Kamal" 1 => "AAA Elmoety" 2 => "YA Rostom" 3 => "MS Shater" 4 => "SA. 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2024 June | 22 | 10 | 32 |
2024 May | 27 | 12 | 39 |
2024 April | 25 | 17 | 42 |
2024 March | 35 | 15 | 50 |
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2024 January | 34 | 15 | 49 |
2023 December | 33 | 21 | 54 |
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2023 August | 39 | 5 | 44 |
2023 July | 24 | 20 | 44 |
2023 June | 23 | 18 | 41 |
2023 May | 33 | 4 | 37 |
2023 April | 26 | 2 | 28 |
2023 March | 11 | 1 | 12 |
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2022 November | 0 | 0 | 0 |