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1.
Ann Surg Oncol ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33751300

RESUMO

BACKGROUND: The aim of this work is to explore the impact of the number of sampling sites (NuSS) and sampling location on microvascular invasion (MVI) detection rate and long-term survival of hepatocellular carcinoma (HCC), and determine the minimum NuSS for sufficient MVI detection. PATIENTS AND METHODS: From January 2008 to March 2017, 1144 HCC patients who underwent hepatectomy were retrospectively enrolled. Associations between NuSS and MVI positive rates and overall survival were investigated. NuSS thresholds were determined by Chow test and confirmed prospectively in 305 patients from April 2017 to February 2019. In the prospective cohort, the distribution of MVI in different sampling locations and its prognostic effect was evaluated. RESULTS: MVI positive rates increased as NuSS increased, steadily reaching a plateau when NuSS reached a threshold. A threshold of four, six, eight, and eight sampling sites within paracancerous parenchyma ≤ 1 cm from tumor was required for detecting MVI in solitary tumors measuring 1.0-3.0, 3.1-4.9, and ≥ 5.0 cm and multiple tumors. Patients with adequate NuSS achieved longer survival than those with inadequate NuSS [hazard ratio (HR) = 0.75, P = 0.043]. For all MVI-positive patients, MVI could be detected positive in paracancerous parenchyma ≤ 1 cm from tumor. Patients with MVI positive in paracancerous parenchyma > 1 cm had higher recurrence risk than those with MVI positive only in parenchyma ≤ 1 cm (HR = 6.05, P < 0.001). CONCLUSIONS: Adequate NuSS is associated with higher MVI detection rate and better survival of HCC patients. We recommend four, six, eight, and eight as the cut-points for evaluating MVI sampling quality and patients' prognostic stratification in the subgroups of solitary tumors measuring 1.0-3.0 cm, 3.1-4.9 cm and ≥ 5.0 cm and multiple tumors, respectively.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33628017

RESUMO

Purpose: Chronic obstructive pulmonary disease (COPD) was the fourth leading cause of death in the world. Many studies have shown that COPD often exists with thyroid dysfunction; however, the relationship between thyroid function and COPD is often ignored in clinical. We retrospectively analyze the serum thyroid hormone levels in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and explore the association between thyroid function and AECOPD. Methods: The study included patients hospitalized for AECOPD in our institution between January 2018 and September 2020. Patients with AECOPD were divided into moderate-to-severe and very severe groups based on lung function, and into normal and abnormal thyroid function groups based on thyroid hormone levels. Collected data and compared data between groups to identify risk factors for thyroid dysfunction in patients with AECOPD. Results: The cohort included 97 in the moderate-to-severe group (72.39%) and 37 in the very severe group (27.61%). Compared with the very severe group, the moderate-to-severe group had higher triglyceride (P=0.017), high-density lipoprotein (P<0.05), partial pressure of carbon dioxide (PaCO2; P<0.05), and serum thyroid-stimulating hormone (TSH; P<0.001). FEV1 as a percentage of the predicted value (FEV1%pred) was positively correlated with TSH and FT3 (r=0.329, r=0.192, respectively, both P<0.05). Duration of hospitalization was negatively correlated with TSH (r=-0.256, P=0.003). Among the 134 subjects, 98 (73.13%) had normal thyroid function and 36 (26.87%) had abnormal thyroid function. The two groups significantly differed regarding forced vital capacity (FVC), forced expiratory volume in 1 second, FEV1%pred, and albumin level. Logistic regression analysis showed that high FVC correlated with a low risk of thyroid dysfunction in AECOPD. Conclusion: In patients with AECOPD, TSH is related to lung function and duration of hospitalization, and high FVC reduces the risk of thyroid dysfunction.

4.
Bioresour Technol ; 323: 124609, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33387709

RESUMO

The aim of this work was to explore the ability of cutinase in the decolorization of molasses wastewater. Thermophilic cutinase from Thermobifida alba eliminated 76.1-78.2% of colorants and exhibited the highest decolorization efficiency amongst all of the cutinases tested. Cutinase from Thermobifida alba was immobilized on an affordable and efficient modified chitosan carrier and achieved a decolorization yield of 79.3-81.2%. This cutinase removed 66.3-71.1% of pigments and lasted continuously for 5 days. Importantly, it was also shown to continuously and effectively remove COD and BOD5. Compared to other enzymes, the immobilized cutinase from Thermobifida alba had the advantage of being low-cost and had a high expression level and activity. The results confirmed the decolorization occurred by destroying the conjugated system of melanoidins via an addition reaction by cutinase from Thermobifida alba. Thus, this study contributes a more practical and efficient approach to enzymatic decolorization of molasses wastewater.


Assuntos
Melaço , Águas Residuárias , Hidrolases
5.
Ecotoxicol Environ Saf ; 208: 111755, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396078

RESUMO

Air pollution constitutes potential threats to wildlife and human health; therefore, it must be monitored accurately. However, little attention has been given to understanding the toxicological effects induced by air pollution and the suitability of bird species as bioindicators. The Eurasian tree sparrow (Passer montanus), a human commensal species, was used as a study model to examine toxic metal accumulation, retention of particulate matter (PM), immunological and antioxidant capacities, and hematological parameters in birds inhabiting those areas with relatively higher (Shijiazhuang city) or lower (Chengde city) levels of PM2.5 and PM10 in China. Our results showed that Shijiazhuang birds had significantly more particle retention in the lungs and toxic metal (including aluminum, arsenic, cadmium, iron, manganese, and lead) accumulation in the feathers relative to Chengde birds. They also had lower superoxide dismutase, albumin, immunoglobulin M concentrations in the lung lavage fluid, and total antioxidant capacity (T-AOC) in the lungs and hearts. Furthermore, although they had higher proportions of microcytes, hypochromia, and polychromatic erythrocytes in the peripheral blood (a symptom of anemia), both populations exhibited comparable body conditions, white cell counts, heterophil and lymphocyte ratios, and plasma T-AOC and corticosterone levels. Therefore, our results not only confirmed that Shijiazhuang birds experienced a greater burden from environmental PM and toxic metals but also identified a suite of adverse effects of environmental pollution on immunological, antioxidative, and hematological parameters in multiple tissues. These findings contribute to our understanding of the physiological health consequences induced by PM exposure in wild animals. They suggest that free-living birds inhabiting urban areas could be used as bioindicators for evaluating the adverse effects induced by environmental pollution.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Poluição Ambiental/estatística & dados numéricos , Pardais/fisiologia , Poluentes Atmosféricos , Animais , Animais Selvagens , Antioxidantes , Cádmio , China , Cidades , Biomarcadores Ambientais , Poluição Ambiental/análise , Plumas , Humanos , Material Particulado , Pardais/sangue
6.
Sci Total Environ ; 754: 142372, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254850

RESUMO

The birds (class Aves) and bats (order Chiroptera, class Mammalia) are well known natural reservoirs of a diverse range of viruses, including some zoonoses. The only extant volant vertebrates, bats and birds have undergone dramatic adaptive radiations that have allowed them to occupy diverse ecological niches and colonize most of the planet. However, few studies have compared the physiology and ecology of these ecologically, and medically, important taxa. Here, we review convergent traits in the physiology, immunology, flight-related ecology of birds and bats that might enable these taxa to act as viral reservoirs and asymptomatic carriers. Many species of birds and bats are well adapted to urban environments and may host more zoonotic pathogens than species that do not colonize anthropogenic habitats. These convergent traits in birds and bats and their ecological interactions with domestic animals and humans increase the potential risk of viral spillover transmission and facilitate the emergence of novel viruses that most likely sources of zoonoses with the potential to cause global pandemics.


Assuntos
Quirópteros , Vírus , Animais , Aves , Reservatórios de Doenças , Humanos , Zoonoses
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 2011-2016, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283734

RESUMO

OBJECTIVE: To investigate the genotype distribution of thalassemia in the population of childbearing age in Yulin area. METHODS: The polymerase reaction (PCR) combined with agargel eletrophoresis and reserve dot bolt hybridization was used to detected the α- and ß-thalassemia gene in 31 769 cases of suspected thalassemia population at childbearing-age. RESULTS: A total of 22 254 cases were identified as thalassemia gene detetion or mutation in 31 769 cases with a detecting rate of 70.05%, and the detecting rate of α-thalassemia, ß-thalassemia and α-combining ß-thalassemia were 45.86% (14 569/31 769), 19.45% (6 178/31 769) and 4.74% (1 507/31 769) respectively. 28 kinds of α-thalassemia gene mutations were detected, the common mutations were as follows: --SEA/αα (28.18%), -α3.7/αα (6.29%), -α4.2/αα (3.66%), αCSα/αα (1.93%) and αWSα/αα (1.89%),and including two rare gene mutations: -THAI and HKαα. 16 kinds of ß-thalassemia gene mutations were detected, the common mutations were as follows: ß41-42/ßN (9.41%), ß-28/ßN (3.05%), ß-17/ßN (2.86%) and ß654/ßN (2.18%). 93 kinds of α combining ß-thalassemia gene mutations were detected, the common mutations were as follows: --SEA/αα (1.05%) and -α3.7/αα (0.56%) combining ß41-42/ßN. CONCLUSION: The detection rate of thalassemia gene is high in Yulin caildbearing-age population, and there is diversity in mutation spectrums of thalassemia. The most common genotypes are --SEA/αα in α-thalassemia and ß41-42/ßN in ß-thalassemia. The results are beneficial for the intervention and genetic consultation of thalassemia.

9.
Science ; 370(6517): 669, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33154129
10.
Dev Comp Immunol ; : 103909, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33129882

RESUMO

Mre11A is considered as a cytosolic DNA receptor in mammals. However, it is rarely known about Mre11A in other vertebrates. Recently, a mammalian ortholog of Mre11A has been identified in grass carp (Ctenopharyngodon idellus) in our lab. Phylogenetic-tree analysis provided evidence for a close genetic relationship between C.idellus Mre11A and Carassius auratus Mre11A. The tissue expression profile of CiMre11A was detected, with a relatively higher level of expression in kidney, intestines, liver and spleen than that in other tissues after grass carp reovirus (GCRV) infection. Similarly, CiMre11A was also up-regulated in CIK cells after treatment with GCRV. Q-PCR and dual-luciferase assays indicated that the transcription levels of IFN1 and ISG15 were inhibited by CiMre11A knockdown, but were gradually augmented after CIK cells were transfected with increasing amounts of CiMre11A. Subcellular localization assays showed that a part of CiMre11A was translocated from the nucleus to the cytoplasm. Co-immunoprecipitation and co-localization assays demonstrated that CiMre11A interacts with CiSTING in response to GCRV infection. In CIK cells, the expressions of both IFN1 and ISG15 were acutely up-regulated by CiMre11A overexpression, as well as by co-overexpression of CiMre11A and CiSTING. CiMre11A and CiSTING induced the phosphorylation and cytoplasmic-to-nuclear translocation of IRF7 in CIK cells. The multiplication of GCRV in CIK cells was inhibited by the overexpression of CiMre11A and CiSTING.

11.
Food Funct ; 11(11): 9881-9891, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33094308

RESUMO

Cooked rice (CR) is a staple diet for many people, but exhibits the high glycemic index that makes it difficult to control the blood glucose. Herein, instant green tea (IGT), instant black tea (IBT) and matcha (Mat) (1, 2 and 3% w/w, rice basis) were added to lower the in vitro starch digestibility and improve the eating quality of CR prepared with an electric rice cooker. The results showed that adding tea products at each level could remarkably reduce the in vitro starch digestibility of CR. Compared with IGT and IBT, 3% of Mat significantly decreased the contents of rapidly digestible starch (RDS) from 72.96% to 60.99%, the digestion rate constant (K) from 11.4 × 10-2 to 8.68 × 10-2 min-1 and the expected glycemic index (eGI) from 77.55 to 66.86. Furthermore, the gas chromatography-ion migration spectrum was analysed to confirm that the tea products endowed the cooked rice with a refreshing flavor by inducing the redistribution of the main aroma components. Moreover, it was found that increasing the ordered crystal structure of rice grains played a major role on lowering the starch digestion, which was demonstrated by the results of the Rapid Visco Analyser, scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. These findings suggested that cooking rice with tea products, especially Mat, can be useful in enhancing the palatability and slowing the in vitro digestion properties of CR.

12.
J Cell Mol Med ; 24(20): 12008-12019, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32896989

RESUMO

The role of the LMNA gene in the development and progression of hepatocellular carcinoma (HCC) and the associated molecular mechanism is not yet clear. Therefore, the purpose of this study was to evaluate the relationship between LMNA and HCC. LMNA gene expression in normal tissues and corresponding tumours was evaluated and the Kaplan-Meier survival analysis was performed. Next, the LMNA gene was knocked out in the 293T and HepG2 cell lines using the CRISPR/Cas9 technique. Subsequently, the proliferation, migration and colony formation rate of the two LMNA knockout cell lines were analysed. Finally, the molecular mechanism affecting the tumorigenesis due to the loss of the LMNA gene was evaluated. The results showed that the LMNA gene was abnormally expressed in many tumours, and the survival rate of the HCC patients with a high expression of the LMNA gene was significantly reduced compared with the rate in patients with a low LMNA expression. The knockout of the LMNA gene in the HCC cell line HepG2 resulted in a decreased tumorigenicity, up-regulation of the P16 expression and down-regulation of the CDK1 expression. These findings suggested that LMNA might function as an oncogene in HCC and provided a potential new target for the diagnosis and treatment of HCC.

13.
Plant Methods ; 16: 107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32782454

RESUMO

Phenotypic information is of great significance for irrigation management, disease prevention and yield improvement. Interest in the evaluation of phenotypes has grown with the goal of enhancing the quality of fruit trees. Traditional techniques for monitoring fruit tree phenotypes are destructive and time-consuming. The development of advanced technology is the key to rapid and non-destructive detection. This review describes several techniques applied to fruit tree phenotypic research in the field, including visible and near-infrared (VIS-NIR) spectroscopy, digital photography, multispectral and hyperspectral imaging, thermal imaging, and light detection and ranging (LiDAR). The applications of these technologies are summarized in terms of architecture parameters, pigment and nutrient contents, water stress, biochemical parameters of fruits and disease detection. These techniques have been shown to play important roles in fruit tree phenotypic research.

15.
Integr Zool ; 15(6): 533-543, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32627943

RESUMO

On the Qinghai-Tibet Plateau, extreme environmental conditions have imposed intense selective pressure on the evolution of phenotypic traits of wild animals. To date, limited information is available on behavioral and ecological traits concerning niche differentiation among sympatric animals on the Qinghai-Tibet Plateau, especially during winter when the environments are most severe. Here, we studied the seasonal variations in habitat occurrence, territorial behavior, and diet in two sympatric snow finches (the white-rumped snow finch, Onychostruthus taczanowskii, WRSF; and the rufous-necked snow finch, Pyrgilauda ruficollis, RNSF) to determine convergence and divergence of ecological traits in such severe climatic conditions. Our results showed that: (i) WRSF occupied rural areas as a dominant species throughout the annual cycle while RNSF occupied the rural areas in summer and then shifted to human-occupied areas in winter and spring; (ii) WRSFs exhibited robust aggressive behavior and territoriality during winter relative to RNSFs; (iii) the diets of both species varied with the season but did not vary between species except that WRSF ate significantly more seeds but RNSF consumed more starchy material derived from human food waste during winter. Therefore, the separations in the spatial niche and territoriality between WRSF and RNSF, especially in winter, may contribute to alleviating the pressure of interspecific competition, and promoting the coexistence of the two sympatric snow finches in the extreme environments on the Qinghai-Tibet Plateau.

16.
Pulm Pharmacol Ther ; 62: 101921, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32615160

RESUMO

BACKGROUND: Bergenin, a type of polyphenol compound, exhibits antiulcerogenic, anti-inflammatory, antitussive, and burn wound-healing properties. However, its therapeutic effect on tumor necrosis factor α (TNF-α)-induced proinflammatory responses in the airway and potential mechanisms of actions are still unclear. This study aimed to investigate the anti-inflammatory effects and mechanism of bergenin in TNF-α-stimulated human bronchial epithelial (16-HBE) cells. METHODS: Cell Counting Kit-8 was used to evaluate cytotoxicity. Cytokine expression was analyzed by reverse transcription-quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay. Immunofluorescence, western blot, and sirtuin-1 (SIRT1) activity assays were employed to investigate potential molecular mechanisms. RESULTS: Bergenin obviously decreased both mRNA and protein expression levels of interleukins 6 and 8 (IL-6 and IL-8) in TNF-α-stimulated 16-HBE cells. Bergenin blocked TNF-α-mediated activation of nuclear factor κB (NF-κB) signaling and NF-κB nuclear translocation. Interestingly, RT-qPCR and western blotting results revealed that bergenin did not affect SIRT1 expression, but significantly increased its activity. Bergenin-mediated SIRT1 activation was further confirmed by results indicating decreased acetylation levels of NF-κB-p65 and p53. Moreover, the inhibitory effects of bergenin on mRNA and protein expression levels of IL-6 and IL-8 were reversed by a SIRT1 inhibitor. In addition, combining bergenin and dexamethasone (DEX) yielded additive effects on the reduction of IL-6 and IL-8 expression. CONCLUSIONS: These findings demonstrate that bergenin could suppress TNF-α-induced proinflammatory responses by augmenting SIRT1 activity to block the NF-κB signaling pathway, which may provide beneficial effects for the treatment of airway inflammation associated with asthma.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32547486

RESUMO

Reproduction is an energetically costly phenomenon. Therefore, to optimize reproductive success, male birds invest enough energetic resources for maintaining well-developed testes. The hypothalamic-pituitary-thyroid (HPT) axis in birds can crosstalk with the hypothalamic-pituitary-gonadal (HPG) axis, thus orchestrating both the reproduction and metabolism. However, until now, how the free-living birds timely optimize both the energy metabolism and reproduction via HPT-axis is not understood. To uncover this physiological mechanism, we investigated the relationships among body mass, testis size, plasma hormones including thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), metabolites including glucose (Glu), triglyceride (TG), total cholesterol (TC), uric acid (UA), diencephalon mRNA expressions of type 2 (Dio2) and 3 (Dio3) iodothyronine deiodinase enzymes, thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), gonadotropin-releasing hormone I (GnRH-I), and gonadotropin-inhibitory hormone (GnIH) in a male Eurasian tree sparrow (ETS, Passer montanus). We found significantly larger testis size; elevated diencephalon Dio2 and TRH mRNA expressions, plasma T3, and UA levels; and significantly lowered Glu, TG, and TC levels during mating relative to the non-mating stages in male ETSs. However, Dio3, TSH, GnRH-I, and GnIH mRNA expression did not vary with the stage. Furthermore, life-history stage dependent variation in plasma T3 had both direct effects on the available energy substrates and indirect effects on body mass and testis size, indicating a complex regulation of metabolic pathways through the HPT- and HPG-axes. The identified differences and relationships in mRNA expression, plasma T3 and metabolites, and testis size in male ETSs contribute to our understanding how free-living birds adjust their molecular, endocrinal, and biochemical features to orchestrate their reproductive physiology and metabolism for the maintenance of well-developed testes.

18.
Pol J Microbiol ; 69(2): 217-222, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32548990

RESUMO

Clinical diagnosis of hepatitis E viral (HEV) infection mainly relies on serological assays, and the current status of misdiagnoses regarding HEV infection is uncertain. In this study, patients with acute HEV infection were tested for anti-HEV IgM and IgG, a HEV antigen (Ag), and viral loads (HEV RNA). Serology was performed using four commercial HEV ELISA kits: Wantai, Kehua, Lizhu, and Genelabs IgM and IgG. The HEV RNA was detected using RT-PCR assays. The sensitivities of different kits for anti-HEV IgM ranged from 82.6% to 86%. Each kit for anti-HEV IgM was highly specific (97.8-100%). The sensitivities of all kits to detect anti-HEV IgG with (87.2-91.9%) had a substantial agreement, but the Kehua and Genelabs tests were more specific than the Wantai and Lizhu tests. The Wantai tests for the HEV Ag and HEV RNA were also important for acute HEV infections (Kappa = 0.787). Furthermore, a total of 6.98% of HEV infections were positive for HEV RNA but negative for both the HEV Ag and anti-HEV antibodies of IgM and IgG classes. Our findings demonstrate that the diagnosis of hepatitis E may be missed if only serological assays are used. Thus, a combination of serological and nucleic acid testing provides the optimal sensitivity and specificity to the diagnostic process.Clinical diagnosis of hepatitis E viral (HEV) infection mainly relies on serological assays, and the current status of misdiagnoses regarding HEV infection is uncertain. In this study, patients with acute HEV infection were tested for anti-HEV IgM and IgG, a HEV antigen (Ag), and viral loads (HEV RNA). Serology was performed using four commercial HEV ELISA kits: Wantai, Kehua, Lizhu, and Genelabs IgM and IgG. The HEV RNA was detected using RT-PCR assays. The sensitivities of different kits for anti-HEV IgM ranged from 82.6% to 86%. Each kit for anti-HEV IgM was highly specific (97.8­100%). The sensitivities of all kits to detect anti-HEV IgG with (87.2­91.9%) had a substantial agreement, but the Kehua and Genelabs tests were more specific than the Wantai and Lizhu tests. The Wantai tests for the HEV Ag and HEV RNA were also important for acute HEV infections (Kappa = 0.787). Furthermore, a total of 6.98% of HEV infections were positive for HEV RNA but negative for both the HEV Ag and anti-HEV antibodies of IgM and IgG classes. Our findings demonstrate that the diagnosis of hepatitis E may be missed if only serological assays are used. Thus, a combination of serological and nucleic acid testing provides the optimal sensitivity and specificity to the diagnostic process.


Assuntos
Ensaio de Imunoadsorção Enzimática/normas , Hepatite E/diagnóstico , Kit de Reagentes para Diagnóstico/normas , Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/genética , Humanos , RNA Viral/análise , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Clin Cancer Res ; 26(18): 4947-4957, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32527942

RESUMO

PURPOSE: Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms. EXPERIMENTAL DESIGN: We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated genomic and immune heterogeneity among tumors through whole-genome sequencing and RNA sequencing. IHC was performed to validate the expression of immune markers. The responses to anti-programmed cell death protein-1 (PD-1) therapy in patients with multifocal hepatocellular carcinoma were evaluated. RESULTS: The small and large tumors within the same patient presented with similar genomic characteristics, indicating their same genomic origin. We further found the small tumors had higher immune cell infiltration including more CD8+ T cells, M1 macrophages, and monocytes as compared with large tumors. Besides, the expression of interferon signature predictive of response to anti-PD-1 therapy was significantly upregulated in the small tumors. Moreover, the immune pathways were more vigorous along with less active proliferation pathways in the small tumors. In keeping with this, we found that small nodules were more sensitive to anti-PD-1 therapy than large nodules in patients with multifocal hepatocellular carcinoma. CONCLUSIONS: The small tumors in patients with multifocal hepatocellular carcinoma had higher immune cell infiltration and upregulation of immune pathways as compared with the large tumors, which can partially explain the different responses of small and large tumors in the same case to anti-PD-1 therapy.

20.
Ann Surg Oncol ; 27(10): 3740-3753, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32424586

RESUMO

BACKGROUND: Postsurgical recurrence is common in early-stage hepatocellular carcinoma (HCC). Prolonged time to surgery (TTS) may lead to tumor progression. However, the impact of TTS on HCC prognosis is controversial in Western studies and unknown in China. We aim to investigate the impact of TTS on the prognosis of Chinese HCC patients at Barcelona Clinic Liver Cancer (BCLC) stage 0-A who underwent surgery. PATIENTS AND METHODS: We retrospectively enrolled 967 BCLC 0-A HCC patients who underwent surgery at three tertiary centers in China. Primary outcomes were recurrence-free survival (RFS) and overall survival (OS). Restricted cubic spline (RCS) was used to select the cutoff value of TTS. Propensity score matching (PSM) was performed to reduce confounding bias, and a time-dependent Cox model was utilized to investigate factors influencing TTS. RESULTS: The median TTS of BCLC 0-A HCC patients was 13 days (interquartile range: 10-21 days). For patients with TTS ≤ 70 days, the cutoff value of TTS was 13 days according to RCS. After PSM, corresponding 1-, 3-, and 5-year RFS of the TTS > 13 days and TTS ≤ 13 days groups were 75.6%, 55.3%, 46.4% and 71.2%, 52.3%, 38.8%, respectively (P = 0.103). Corresponding 1-, 3-, and 5-year OS of TTS > 13 days and TTS ≤ 13 days groups were 93.7%, 82.8%, 69.6% and 92.4%, 78.5%, 68.4%, respectively (P = 0.580). Time-dependent Cox analysis revealed that age and tumor size were factors influencing TTS. CONCLUSIONS: Our study suggests that, for patients with TTS ≤ 70 days, prolonged TTS had no impact on BCLC 0-A Chinese HCC patients receiving surgery.

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