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1.
J Infect Dis ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32211776

RESUMO

BACKGROUND: Safe nucleos(t)ide analogue discontinuation in chronic hepatitis B (CHB) is an unmet need. We aimed to investigate whether combining HBV RNA and hepatitis B core-related antigen (HBcrAg) could perform satisfactorily in predicting off-treatment outcomes. METHODS: The evaluation cohort included 127 HBeAg-positive patients from a multi-centre prospective trial who stopped telbivudine-based therapy after achieving HBeAg seroconversion and HBV DNA<50 IU/mL for >48 weeks. As validation, 59 patients treated with entecavir or tenofovir before discontinuation were analysed. RESULTS: At the end of treatment (EOT), HBV RNA and HBcrAg were significant independent predictors of the clinical relapse risk. In the evaluation cohort, no clinical relapse occurred among patients with negative HBV RNA and HBcrAg <4 log10 U/mL at EOT (low-risk group), whereas 46.8% patients with positive HBV RNA and HBcrAg ≥4 log10 U/mL (high-risk group) experienced clinical relapse during 4-year post-treatment follow-up (P <0.001); the corresponding incidences in the validation cohort were 0% and 69.4% (P <0.001), respectively. More patients in the low-risk group achieved HBsAg loss than the other patients after treatment cessation (16.1% vs. 1.3%, P =0.002). CONCLUSION: Combining HBV RNA and HBcrAg performed satisfactorily in predicting clinical relapse and HBsAg loss after treatment cessation in HBeAg-positive CHB patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31999093

RESUMO

Graphitic carbon nitride (gCN) has a broad range of promising applications, from energy harvesting and storage to sensing. However, most of the applications are still restricted due to gCN poor dispersibility and limited functional groups. Herein, a direct photografting of gCN using various polymer brushes with tailorable functionalities via UV photopolymerization at ambient conditions is demonstrated. The systematic study of polymer brush-functionalized gCN reveals that the polymerization did not alter the inherent structure of gCN. Compared to the pristine gCN, the gCN-polymer composites show good dispersibility in various solvents such as water, ethanol, and tetrahydrofuran (THF). Patterned polymer brushes on gCN can be realized by employing photomask and microcontact printing technology. The polymer brushes with incorporated silver nanoparticles (AgNPs) on gCN can act as a multifunctional recyclable active sensing layer for surface-enhanced Raman spectroscopy (SERS) detection and photocatalysis. This multifunctionality is shown in consecutive cycles of SERS and photocatalytic degradation processes that can be applied to in situ monitor pollutants, such as dyes or pharmaceutical waste, with high chemical sensitivity as well as to water remediation. This dual functionality provides a significant advantage to our AgNPs/polymer-gCN with regard to state-of-the-art systems reported so far that only allow SERS pollutant detection but not their decomposition. These results may provide a new methodology for the covalent functionalization of gCN and may enable new applications in the field of catalysis, biosensors, and, most interestingly, environmental remediation.

3.
Adv Mater ; 32(4): e1905681, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31788883

RESUMO

The intrinsic advantages of metallic Zn, like high theoretical capacity (820 mAh g-1 ), high abundance, low toxicity, and high safety have driven the recent booming development of rechargeable Zn batteries. However, the lack of high-voltage electrolyte and cathode materials restricts the cell voltage mostly to below 2 V. Moreover, dendrite formation and the poor rechargeability of the Zn anode hinder the long-term operation of Zn batteries. Here a high-voltage and durable Zn-graphite battery, which is enabled by a LiPF6 -containing hybrid electrolyte, is reported. The presence of LiPF6 efficiently suppresses the anodic oxidation of Zn electrolyte and leads to a super-wide electrochemical stability window of 4 V (vs Zn/Zn2+ ). Both dendrite-free Zn plating/stripping and reversible dual-anion intercalation into the graphite cathode are realized in the hybrid electrolyte. The resultant Zn-graphite battery performs stably at a high voltage of 2.8 V with a record midpoint discharge voltage of 2.2 V. After 2000 cycles at a high charge-discharge rate, high capacity retention of 97.5% is achieved with ≈100% Coulombic efficiency.

4.
Clin Gastroenterol Hepatol ; 18(3): 719-727.e7, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31362119

RESUMO

BACKGROUND & AIMS: There is no satisfactory way to identify patients who will maintain a response after discontinuation of nuleos(t)ide analogue therapy for chronic hepatitis B virus (HBV) infection. We investigated whether patients with negative results from tests for HBV DNA and HBV RNA (double negative) at the end of treatment maintain a long-term response to treatment. METHODS: We performed a post-hoc analysis of data from a 2-year multi-center randomized controlled trial, and its long-term extension trials, on 130 patients with chronic HBV infection who were positive for the HB e antigen (HBeAg-positive; mean age, 30.8 ± 6.9 years; 72.3% male) and received telbivudine with or without adefovir and stopped therapy after they had HBeAg seroconversion and levels of HBV DNA <300 copies/mL for at least 48 weeks (evaluation cohort). Clinical and laboratory assessments were made every 12 or 16 weeks until clinical relapse (defined as HBV DNA > 2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) or until 4 years off treatment. We validated our findings in a cohort of 40 HBeAg-positive patients (36.5 ± 9.4 years old; 72.5% male) treated with entecavir or tenofovir, and followed after discontinuation for up to 5.5 years. Patients were considered to be negative for HBV DNA if it was not detected in the COBAS Taqman assay. Patients were considered to be negative for HBV RNA if it was not detected by quantitative real-time PCR with 2 different pairs of primers. RESULTS: After 4 years off treatment, in the evaluation cohort, 30.8% of patients had a clinical relapse, 54.7% had virologic relapse (HBV DNA >2000 IU/mL in 2 tests), and 16.8% had reappearance of HBeAg in 2 tests (reversion). A significantly lower proportion of double negative patients had a clinical relapse 4 years later (2/35; 8.0%) than of patients who tested positive for either HBV DNA or RNA (32/102; 31.4%; P = .018). In the validation cohort, after 5.5 years of follow up, a lower proportion of double negative patients had clinical relapse (2/13; 15.4%) than of patients who tested positive for either HBV DNA or RNA at the end of treatment (9/27; 33.3%; P = .286) CONCLUSIONS: In an analysis of data from 2 independent cohorts, we associated negative results from tests for HBV DNA and RNA (double negative) at the end of treatment with continued response 4 or more years after discontinuation of therapy in HBeAg-positive patients. These results might be used to identify the best candidates for discontinuation of nuleos(t)ide analogue therapy.

5.
Clin Gastroenterol Hepatol ; 18(2): 457-467.e21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31306800

RESUMO

BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31693399

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer in adults. Previous studies in our lab found that long non-coding RNA (lncRNAs) Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) was up regulated in HCC cells, which could affect the metastasis and invasion of HCC. However, the detailed mechanism remains unknown. Here, we studied the interaction between MALAT1 and miR-140 on the regulation of angiogenesis and immunosuppressive properties of HCC cells. METHODS: Quantitative real-time PCR was employed to assess the expression of MALAT1, miR-140, IL-6, IL-10 and VEGF-A. Flow cytometry was used to measure the polarization of macrophage. Western blot was used to assess the expressions of VEGF-A. Dual-luciferase reporter assay was performed to verify the interaction between MALAT1 and miR-140 or miR-140 and VEGF-A. Tube formation assay was performed to determine the angiogenetic ability of Human Umbilical Vein Endothelial Cells (HUVECs). Transwell assay was used to assess the migration of HUVECs. RESULTS: Knockdown of MALAT1 in HCC cells could suppress the production of VEGF-A, impair the angiogenesis of HUVECs and facilitate the polarization of macrophage towards M1 subset. Mechanistically, the interaction between MALAT1 and miR-140 or between miR-140 and VEGF-A was confirmed by multiple assays. Furthermore, miR-140 inhibition significantly increased VEGF-A expression, promoted angiogenesis of HUVECs and re-directed the polarization of macrophage towards M2 subset. CONCLUSIONS: In summary, this study revealed the mechanisms by which MALAT1 worked as a putative HCC promotor via inhibiting miR-140. Therefore, targeting MALAT1 or miR-140 might alleviate the progression of HCC in future.

7.
Ann Transl Med ; 7(18): 449, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31700885

RESUMO

Background: To investigate the association of plasma miR-146a with serological conversion of hepatitis B e-antigen (HBeAg) in patients with chronic hepatitis B (CHB) treated with nucleotide analogs (NAs). Methods: This was a retrospective study of 115 HBeAg-positive patients with CHB treated at Xiangya Hospital, Central South University, Changsha, China, between September 2009 and March 2014. Patients were grouped according to whether they had achieved seroconversion of HBeAg by 104 weeks of NAs treatment. We assessed plasma miR-146a using miScript polymerase chain reaction (PCR). Serum alanine transaminase (ALT), hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load, hepatitis B surface antigen (HBsAg) titer, HBeAg titer, and plasma miR-146a were measured at 0, 24, 48, and 104 weeks of treatment. Finally, we also determined ΔmiR-146a24w and ΔmiR-146a48w. Results: ΔmiR-146a48w was independently associated with seroconversion of HBeAg at 104 weeks [odds ratio (OR) =1.302; 95% confidence interval (CI), 1.159-1.962; P=0.029]. We obtained an area under the receiver operating characteristic (ROC) curve (AUC) of ΔmiR-14648w of 0.757 for seroconversion of HBeAg (P=0.013). At the optimal cutoff value equivalent to a Youden index of 67.9%, the specificity and sensitivity of ΔmiR-14648w were 63.7% and 88.3%, respectively. Positive (PPV) and negative (NPV) predictive values were 70.87% and 84.48%, respectively. Conclusions: ΔmiR-146a48w was independently associated with seroconversion of HBeAg in CHB patients treated with NAs.

8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(8): 845-849, 2019 Aug 28.
Artigo em Chinês | MEDLINE | ID: mdl-31570669

RESUMO

OBJECTIVE: To detect the levels of miR-146a and miR-155 in different samples from chronic hepatitis B (CHB), reveal whether there is a correlation between the 2 miRNAs in different samples, and to provide a theoretical basis for sample choice of miRNA research in liver.
 Methods: Real-time PCR was conducted to examine the expression of miR-146a and miR-155 in the plasma, peripheral blood mononuclear cell (PBMC), and liver tissues from 41 CHB patients who underwent nucleoside analogues antiviral therapy for 104 weeks. Correlations between the levels of miR-146a and miR-155 among the 3 samples were analyzed.
 Results: The expressions of miR-146a and miR-155 in the plasma, PBMC and liver tissues were significantly down-regulated at the 104th week than those at the baseline (all P<0.05). There was a correlation in the expression of miR-146a between plasma and liver tissues (r=0.560, P=0.007), PBMC and liver tissues (r=0.428, P=0.047) at baseline. There was a correlation in the expression of miR-155 between plasma and liver tissue (r=0.587, P=0.004), PBMC and liver tissue (r=0.483, P=0.023) at baseline. The expressions of miR-146a and miR-155 between the plasma and PBMC were not correlated (P>0.05).
 Conclusion: Compared with PBMC, miR-146a and miR-155 from plasma can better reflect the expression in the liver tissues, suggesting that plasma can be applied in the mechanism research on miR-146a and miR-155 in the liver diseases instead of liver tissues.


Assuntos
Hepatite B Crônica , MicroRNAs/genética , Hepatite B Crônica/genética , Humanos , Leucócitos Mononucleares , Reação em Cadeia da Polimerase em Tempo Real
9.
J Biosci ; 44(4)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502570

RESUMO

Radioresistance is a material obstacle for effective treatment of colorectal cancer (CRC). Thus, the discovery of a novel biomarker for determining the CRC radiosensitivity is necessary. Recent studies have confirmed that miR-183-3p regulates cell phenotypes and tumor growth in various cancers. However, the role and mechanism of this micro-ribonucleic acid in CRC radiosensitivity remains unclear. Here, the abundances of miR-183-5p and ATG5 mRNAwere detected by a real-time quantitative reverse transcription polymerase chain reaction. Kaplan-Meier survival analysis was carried out to explore the correlation between miR-183-5p and patient prognosis. Cell viability was evaluated by the MTT assay. Survival fraction analysis through colony formation was performed to assess the cell radiation response. Bioinformatic, luciferase and western blot assays were employed to verify the targeted interaction between miR-183-5p and ATG5. The results showed that an elevated abundance of miR-183-5p and a reduced ATG5 level in CRC were associated with the poor prognosis. The knockdown of miR-183-5p enhanced the sensitivity of CRC cells to radiation, inflected by the decreased cell viability and survival fraction. Mechanically, ATG5 was targeted by miR-183-5p. The addition of ATG5 conferred the radiosensitivity of the CRC cells, which was revered by miR-183-5p restoration. Furthermore, miR-183-5p knockdown hindered the tumor growth by repressing ATG5 in vivo after radiation treatment. In summary, the output data indicated that miR-183-5p heightened the radiation response of the CRC cells by targeting ATG5, promising a novel therapeutic target for CRC patients with radioresistance.


Assuntos
Proteína 5 Relacionada à Autofagia/genética , Neoplasias Colorretais/radioterapia , MicroRNAs/genética , Tolerância a Radiação/genética , Idoso , Sobrevivência Celular/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Cell Mol Med ; 23(11): 7517-7524, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31512358

RESUMO

Mesenchymal stem cells (MSCs) have potential ability to differentiate into osteocytes in response to in vitro specific induction. However, the molecular basis underlying this biological process remains largely unclear. In this study, we identify lncRNA HOTAIRM1 as a critical regulator to promote osteogenesis of MSCs. Loss of HOTAIRM1 significantly inhibits the calcium deposition and alkaline phosphatase activity of MSCs. Mechanistically, we find that HOTAIRM1 positively modulates the activity of JNK and c-Jun, both of which are widely accepted as crucial regulators of osteogenic differentiation. More importantly, c-Jun is found to be functionally involved in the regulation of RUNX2 expression, a master transcription factor of osteogenesis. In detail, c-Jun can help recruit the acetyltransferase p300 to RUNX2 promoter, facilitating acetylation of histone 3 at K27 site, therefore epigenetically activating RUNX2 gene transcription. In summary, this study highlights the functional importance of HOTAIRM1 in regulation of osteogenesis, and we characterize HOTAIRM1 as a promising molecular target for bone tissue repair and regeneration.

11.
Hepatol Int ; 13(5): 573-586, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172415

RESUMO

BACKGROUND: Switching from nucleos(t)ide analogues to interferon (IFN) improves hepatitis B surface antigen (HBsAg) loss. We aimed to evaluate whether combining immunomodulators such as interleukin-2 (IL-2) and therapeutic vaccine with IFN enhances HBsAg loss in entecavir (ETV)-suppressed patients. METHODS: Ninety-four patients exhibiting virological suppression and hepatitis B e antigen (HBeAg) loss following ETV treatment were randomized 1:1:1 to receive ETV (group I) or IFN (group II) for 48 weeks, or IFN and vaccine for 48 weeks plus IL-2 for 12 weeks (group III). The primary endpoint was HBsAg loss at week 48. Peripheral natural killer (NK) cells and regulatory T cells (Treg) were measured as immune checkpoint indicators. RESULTS: Mean HBsAg decline at week 48 was significantly greater in group III (0.85 log 10 IU/mL) and group II (0.74 log 10 IU/mL), than in group I (0.13 log 10 IU/mL). At week 48, 9.38%, 3.03%, and 3.70% of subjects in group III, II, and I, respectively, achieved HBsAg loss. Among patients with baseline HBsAg titers ranging from 100 to 1500 IU/mL, HBsAg loss rate was 27.3, 7.1, and 0% in group III, II, and I, respectively. Responders in group III showed a significantly higher increase in CD56bright CD16-NK cells from week 24 to 36, and a significant decline in Treg from week 12 to 24 than non-responders. CONCLUSION: For ETV-suppressed patients, particularly those with low baseline HBsAg levels, combination therapy with IFN and other immunomodulators may enhance HBsAg loss, while successful response correlates with partial restoration of NK cells and Tregs.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Vacinas contra Hepatite B/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferons/uso terapêutico , Interleucina-2/uso terapêutico , Adulto , Antivirais/administração & dosagem , Terapia Combinada , Quimioterapia Combinada , Feminino , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Humanos , Interferons/administração & dosagem , Interleucina-2/administração & dosagem , Masculino
12.
Hepatol Int ; 13(3): 260-269, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30977033

RESUMO

BACKGROUND AND AIM: Long-term treatment with tenofovir disoproxil fumarate (TDF) has demonstrated suppression of viral replication outside of China. This study aims to assess efficacy, resistance and safety of TDF for up to 240 weeks in Chinese patients with chronic hepatitis B virus (HBV) infection. METHODS: Patients (HBeAg-positive or HBeAg-negative) who were randomised to receive TDF 300 mg or adefovir dipivoxil (ADV) 10 mg once daily in the 48-week double-blind phase (N = 498) were eligible to enter the open-label TDF phase (TDF-TDF and ADV-TDF groups) for additional 192 weeks. RESULTS: Overall, 457/512 (89.3%) randomised patients completed 240 weeks of treatment. Virological suppression was achieved in 84.5% and 87.9% in HBeAg-positive patients and 89.6% and 89.5% in HBeAg-negative patients in TDF-TDF and ADV-TDF groups, respectively, at week 240. The majority of patients from both groups had normalized alanine transaminase levels. More patients had HBeAg loss (41.7% vs. 36.4%) and HBeAg seroconversion (32.0% vs. 28.3%) in TDF-TDF than in ADV-TDF group, respectively. Only one HBeAg-positive patient in TDF-TDF group had HBsAg loss at week 240. No evidence of resistance to TDF was observed. The incidence of adverse events was similar in both groups (TDF-TDF, 56.4% vs. ADV-TDF, 51.6%). One patient had serum creatinine elevation ≥ 0.5 mg/dL above baseline, and three patients had confirmed grade 3/4 phosphorus abnormalities (< 2 mg/dL). CONCLUSION: In Chinese patients with chronic HBV, long-term treatment with TDF showed sustained viral suppression without development of resistance up to 240 weeks. No new safety concerns were found with TDF in this patient population. Clinical Trial Registration ClinicalTrial.gov Identifier NCT01300234; GSK Clinical Study Register 114648.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/efeitos adversos , Grupo com Ancestrais do Continente Asiático , China , Método Duplo-Cego , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tenofovir/efeitos adversos , Carga Viral , Adulto Jovem
13.
ChemSusChem ; 11(24): 4269-4274, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30290060

RESUMO

The aqueous rechargeable lithium battery (ARLB) is one of the most promising devices for large-scale grid applications. Currently, a key issue for ARLBs is to develop promising anode materials with favorable electrochemical performances. Here, for the first time, we demonstrate an aqueous battery that utilizes the reversible redox reaction with hydroxide ions (OH- ) in the hematite (Fe2 O3 ) anode and a commercial Li ion intercalation compound in neutral solution as the cathode. The fabricated aqueous battery displays a reversible capacity of 92 mAh g-1 . The morphology of the used Fe2 O3 anode with exposed {1 0 4} facets for this aqueous battery is unique and attractive. Importantly, with the dual-pH neutral-alkaline hybrid electrolyte, many excellent anode materials that previously could only work in alkaline electrolytes can now be successfully combined with commercial cathodes in neutral solutions, which may significantly enrich the range of anode materials for ARLBs. In addition, the reported battery configuration can be extended to other aqueous batteries beyond Li-ion ones with lower cost.

14.
PLoS One ; 13(7): e0199198, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30016335

RESUMO

BACKGROUND & AIMS: It has yet to be firmly established whether host IFNL3 (IL28B) genotype influences interferon responsiveness in patients with chronic hepatitis B. We investigated associations between single-nucleotide polymorphisms (SNPs) in the IFNL3 region and response to peginterferon alfa-2a in 701 patients enrolled in three large, randomized, international studies. METHODS: Responses were defined as hepatitis B surface antigen (HBsAg) loss and/or hepatitis B e antigen (HBeAg) seroconversion plus hepatitis B virus (HBV) DNA <2000 IU/ml in HBeAg-positive patients, and HBsAg loss and/or HBV DNA <2000 IU/ml in HBeAg-negative patients (24 weeks after end of treatment). Associations between treatment response and the number of copies of the poor-response allele at three SNPs (rs8099917, rs12980275, rs12979860) were explored with logistic regression models in Asian and white patients. RESULTS: The HBeAg-positive and -negative populations comprised 465 (92% Asian, 50% HBV genotype C) and 236 (79% Asian, 41% HBV genotype C) patients, respectively, and had respective response rates of 26% and 47%. The IFNL3 genotype was strongly associated with ethnicity. There was no association between IFNL3 genotype and treatment response in HBeAg-positive or -negative patients. Independent predictors of treatment response were: sex, HBV DNA level and alanine aminotransferase level in HBeAg-positive Asian patients; age in HBeAg-negative Asian patients; and HBV DNA in HBeAg-negative white patients. CONCLUSIONS: This is the largest analysis to date of associations between IFNL3 genotype and peginterferon response in patients with chronic hepatitis B. The data suggest that IFNL3 polymorphism is not a major determinant of the response to peginterferon alfa-2a in either HBeAg-positive or HBeAg-negative patients.


Assuntos
Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Interleucinas/genética , Polietilenoglicóis/uso terapêutico , Adulto , Alanina Transaminase/sangue , Grupo com Ancestrais do Continente Asiático , DNA Viral/antagonistas & inibidores , DNA Viral/genética , DNA Viral/imunologia , Grupo com Ancestrais do Continente Europeu , Feminino , Expressão Gênica , Genótipo , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/etnologia , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Humanos , Interferons , Interleucinas/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(5): 475-480, 2018 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-29886461

RESUMO

OBJECTIVE: To investigate expression profiles of the plasma exosomal miRNAs of the chronic hepatitis B (CHB) patients with persistently normal alamine aminotransferase (PNALT) for the first time and try to find exosomal miRNAs which could reflect liver inflammation better. 
 Methods: Five CHB patients with liver tissue inflammation grade ≥A2 of PNALT and 5 CHB patients with liver tissue inflammation grade

Assuntos
Alanina Transaminase/sangue , Exossomos/metabolismo , Hepatite B Crônica/sangue , MicroRNAs/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Regulação para Baixo , Exossomos/ultraestrutura , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs/análise , Tamanho da Partícula , Regulação para Cima
16.
Hepatobiliary Pancreat Dis Int ; 17(2): 126-132, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29602672

RESUMO

BACKGROUND: Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum miRNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF. METHODS: Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to 30 chronic asymptomatic HBV carriers as controls. The miRNAs expressions were measured by real-time quantitative PCR (q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed miRNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model. RESULTS: Real-time q-PCR indicated that serum miR-146a-5p, miR-122-3p and miR-328-3p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and miR-122-3p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+ - 1.72 × INR - 4.963 × gastrointestinal bleeding (Yes = 0; No = 1)-0.278 × (miR-122-3p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve (AUROC) was 0.847. CONCLUSIONS: Expression levels of these miRNAs (miR-146a-5p, miR-122-3p and miR-328-3p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.


Assuntos
Insuficiência Hepática Crônica Agudizada/sangue , MicroRNA Circulante/sangue , Hepatite B Crônica/sangue , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/genética , Insuficiência Hepática Crônica Agudizada/virologia , Adulto , Área Sob a Curva , Estudos de Casos e Controles , MicroRNA Circulante/genética , Feminino , Hemorragia Gastrointestinal/sangue , Hemorragia Gastrointestinal/genética , Hemorragia Gastrointestinal/virologia , Marcadores Genéticos , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/genética , Hepatite B Crônica/virologia , Humanos , Coeficiente Internacional Normatizado , Modelos Logísticos , Masculino , MicroRNAs , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Sódio/sangue , Regulação para Cima , Adulto Jovem
17.
Adv Mater ; 30(20): e1800533, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29602214

RESUMO

Developing high-power cathodes is crucial to construct next-generation quick-charge batteries for electric transportation and grid applications. However, this mainly relies on nanoengineering strategies at the expense of low scalability and high battery cost. Another option is provided herein to build high-power cathodes by exploiting inexpensive bulk graphite as the active electrode material, where anion intercalation is involved. With the assistance of a strong alginate binder, the disintegration problem of graphite cathodes due to the large volume variation of >130% is well suppressed, making it possible to investigate the intrinsic electrochemical behavior and to elucidate the charge storage kinetics of graphite cathodes. Ultrahigh power capability up to 42.9 kW kg-1 at the energy density of >300 Wh kg-1 (based on graphite mass) and long cycling life over 10 000 cycles are achieved, much higher than those of conventional cathode materials for Li-ion batteries. A self-activating and capacitive anion intercalation into graphite is discovered for the first time, making graphite a new intrinsic intercalation-pseudocapacitance cathode material. The finding highlights the kinetical difference of anion intercalation (as cathode) from cation intercalation (as anode) into graphitic carbon materials, and new high-power energy storage devices will be inspired.

18.
Transfus Apher Sci ; 57(2): 253-258, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29571962

RESUMO

OBJECTIVE: To compare two means of performing therapeutic plasma exchange (TPE) in patients with liver failure. METHOD: This open-label monocentric randomized trial, conducted in a single prestigious general healthcare facility, recruited liver failure patients with an indication to receive artificial liver support therapy for TPE. All patients underwent TPE procedures and were administered in a random sequence: heparin-free or systemic heparinization with unfractionated heparin. The primary endpoint was completion of TPE sessions, and the secondary endpoints included the safety and efficacy. RESULTS: In the period of the studying, there were 164 patients being recruited in and underwent total of 398 randomized TPEs: 168 with unfractionated heparin and 230 with heparin-free. In unfractionated heparin group, there were 3 cases (1.79%) being interrupted due to uncontrollable intraoperative pulmonary hemorrhages and gastrointestinal bleeding. In heparin-free group, 228 (99.13%) were completed successfully and 2 of them (0.87%) were switched from heparin-free to unfractionated heparin eventually. No significant differences were found between the two groups for either RRs or IRs (P > 0.05). CONCLUSION: Heparin-free regimen is feasible and safer than systemic heparinization with unfractionated heparin in the process of TPEs in patients with liver failure.


Assuntos
Falência Hepática/terapia , Troca Plasmática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Hepatol Res ; 48(3): E213-E221, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28834607

RESUMO

AIM: The role of vitamin D in individuals with chronic hepatitis B (CHB) is unclear. We aimed to explore the association of baseline vitamin D level with genetic determinants and week-104 treatment outcome in CHB patients. METHODS: Baseline serum 25-hydroxycholecalciferol (25(OH)D) levels and genetic polymorphism within GC, DHCR7, and CYP2R1 were determined in stored serum of 560 patients who were enrolled into a multicenter, randomized, controlled study and completed 104 weeks of telbivudine monotherapy or telbivudine-based optimized therapy. Virologic response was defined as hepatitis B virus DNA <300 copies/mL (52 IU/mL) at week 104. RESULTS: The mean 25(OH)D value was 29.64 ng/mL. The percentage of patients with vitamin D insufficiency (<30 ng/mL) and vitamin D deficiency (<20 ng/mL) were 55.0% and 20.9%, respectively. Gender, season, latitude, and GC rs2282679 polymorphism were independent factors of vitamin D status. Patients with sufficient vitamin D (≥30 ng/mL) achieved a higher virologic response rate than those with vitamin D insufficiency (81.7% vs. 67.2%, P < 0.001). The area under the curve of 25(OH)D to predict virologic response was 0.65 (P < 0.001; 95% confidence interval, 0.62-0.67). On multivariate analysis, 25(OH)D level was an independent predictor of virologic response, but not associated with hepatitis B envelope antigen (HBeAg) seroconversion or alanine aminotransferase (ALT) normalization. CONCLUSIONS: Vitamin D insufficiency was highly prevalent in treatment-naïve CHB patients in mainland China. Latitude and genetic determinants affect vitamin D status. Baseline vitamin D level can predict week-104 virologic response, but not HBeAg seroconversion or ALT normalization.

20.
Hepatol Res ; 48(2): 134-143, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28422442

RESUMO

AIM: Previous studies have reported that hepatitis B virus (HBV) genotype is not a predictor of treatment response with nucleos(t)ide analog therapy. However, the impact of subgenotype on treatment response is unknown. The aim of this study is to identify the effect of HBV subgenotype on treatment response. METHODS: In this retrospective study, the derivation dataset comprised patients from the EFFORT study (NCT00962533) telbivudine monotherapy group; patients infected with genotypes B or C from the GLOBE (NCT00057265) and 015 (NCT00131742) studies formed the validation dataset. The HBV subgenotypes were determined using phylogenetic analysis based on the surface or overlapping polymerase gene. Molecular modeling was used to investigate relationships between positions of the substitutions within reverse transcriptase and genotypic resistance. RESULTS: Of the patients in the derivation dataset, 110, 24, 162, and 1 patients were classified as having HBV subgenotypes B2, C1, C2, or other, respectively, compared to 222, 146, 282, and 51 in the validation dataset, respectively. Patients infected with subgenotype C1 showed a higher virologic response rate and hepatitis B envelope antigen seroconversion rate, and lower genotypic resistance rate than those infected with subgenotypes B2 and C2. Patients with genotypic resistance to telbivudine with subgenotype C1 showed fewer secondary mutations. The crystal structure model of reverse transcriptase showed that these secondary mutations were located around the YMDD motif, which possibly influenced the chance of mutations at rtM204. CONCLUSION: Hepatitis B virus subgenotype C1 is associated with better antiviral response to nucleoside analogs in hepatitis B envelope antigen-positive patients than B2 and C2 subgenotypes. The exact mechanism needs to be explored further.

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