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1.
Chem Commun (Camb) ; 55(100): 15145-15148, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31790115

RESUMO

A lipase-triggered drug release nanoplatform (PGL-DPP-FLU NPs) for multi-modal antifungal therapy is developed. The lipases secreted by C. albicans can accelerate FLU release. The ROS and heat produced by PGL-DPP-FLU NPs make C. albicans more vulnerable to FLU, thereby PGL-DPP-FLU NPs exhibit high performance for combating azole-resistant C. albicans biofilms and wound infection.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31750262

RESUMO

Gut microbiota composition is known to be associated with the progression of hepatitis B virus (HBV)-related liver cirrhosis in humans, outcome of HBV infection in mice, and seroconversion of HBV e-antigen in nucleot(s)ide analog-treated patients. The dynamic alteration of the gut microbiota following HBV infection is still unknown. In this study, a hydrodynamic injection mouse model mimicking acute or chronic HBV infection in humans with comparable virological and immunological features was used. The composition of gut microbiota in the control mice and mice with acute or chronic HBV infection was analyzed at different time points using the Illumina MiSeq platform. The expression of immune molecules in the colon was detected by real-time polymerase chain reaction. We found that the changes in gut microbiota composition, including the total operational taxonomic unit (OTU) count and Shannon-Weaver index, were significantly delayed in mice with HBV infection. Furthermore, the ratio of Bacteroidetes and Firmicutes was stable in the control mice, whereas remarkable dynamic patterns were observed in mice with HBV infection. Interestingly, the dynamic changes in Lactobacillus and Bifidobacterium were found to differ in acute or chronic HBV infection. In addition, the expression of IFN-γ and PD-L1 in the colon was found to be up-regulated early in mice with acute HBV infection, whereas the expression of PD-L1 in the colon of mice with chronic HBV infection was up-regulated later. These data indicate that HBV infection could hamper the development of the gut microbiota community and dynamically change the gut Firmicutes/Bacteroidetes ratio. These data improve our understanding of the relationship between gut microbiota and HBV infection.

3.
J Clin Transl Hepatol ; 7(3): 213-220, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608212

RESUMO

Background and Aims: Ravidasvir (RDV) is a new generation pangenotypic hepatitis C virus (HCV) NS5A inhibitor, with high barrier to baseline resistance-associated species. This is the first phase 2/3 study conducted in Mainland China confirming the efficacy and safety of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks in treatment-naïve noncirrhotic patients with genotype 1 infection in a large population. Methods: In this multicenter, randomized, double-blinded, placebo-controlled phase 2/3 trial (NCT03362814), we enrolled 424 treatment-naïve, noncirrhotic adult HCV genotype 1 patients. All patients were randomized at 3:1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day (body weight <75/≥75 kg) (n = 318) or placebo (n = 106) for 12 weeks. The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment, and the safety was evaluated and compared between treatment and placebo groups. Results: The overall rate of sustained virological response at 12 weeks after treatment is 99% (306/309, 95%, CI: 97%-100%) under per protocol set analysis. All patients harboring baseline NS5A resistance-associated species in the treatment group (76/76, per protocol set) achieved sustained virological response at 12 weeks after treatment. No treatment-related serious adverse events were reported. Laboratory abnormalities showed mild or moderate severity (grade 1 and grade 2) in liver function tests. Conclusions: In treatment-naïve, noncirrhotic HCV Chinese patients infected with HCV genotype 1, all-oral regimen of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks was highly efficacious, safe, and well tolerated.

4.
J Immunol ; 203(11): 2872-2886, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31636238

RESUMO

TLR2 serves as a costimulatory molecule on activated T cells. However, it is unknown how the functionality and antiviral activity of CD8+ T cells are modulated by direct TLR2 signaling. In this study, we looked at the TLR2-mediated enhancement of TCR-driven CD8+ T cell activation in vitro and in woodchuck hepatitis virus transgenic mice. In vitro stimulation of CD8+ T cells purified from C57BL/6 mice showed that TLR2 agonist Pam3CSK4 directly enhanced the TCR-dependent CD8+ T cell activation. Transcriptome analysis revealed that TLR2 signaling increased expression of bioenergy metabolism-related genes in CD8+ T cells, such as IRF4, leading to improved glycolysis and glutaminolysis. This was associated with the upregulation of genes related to immune regulation and functions such as T-bet and IFN-γ. Glycolysis and glutaminolysis were in turn essential for the TLR2-mediated enhancement of T cell activation. Administration of TLR2 agonist Pam3CSK4 promoted the expansion and functionality of vaccine-primed, Ag-specific CD8+ T cells in both wild type and transgenic mice and improved viral suppression. Thus, TLR2 could promote CD8+ T cell immunity through regulating the energy metabolism.

5.
Discov Med ; 27(150): 235-243, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31421692

RESUMO

In recent years, with the westernization of lifestyle, reduced physical activity and increased prostate-specific antigen (PSA) testing, the incidence of prostate cancer (PCa) has risen significantly in developing countries. Currently, PSA is the only PCa biomarker applied clinically, but it does not perform well in the early diagnosis and distinguishing between benign prostatic hyperplasia and prostate cancer. With the advances in deep sequencing technology, a series of new PCa biomarkers have been recently proposed to improve the diagnostic value of PSA, such as prostate cancer antigen 3 (PCA3), TMPRSS2-ETS fusion gene, microRNA, and other regulatory non-coding RNAs. In addition, the prostate health index (PHI) has been approved by the U.S. Food and Drug Administration (FDA) for clinical use in the detection of PCa. The prostate-specific membrane antigen (PSMA) has been confirmed to be specifically expressed on the surface of PCa cells. In this review, we provide an updated summary of the value and features of these novel biomarkers in the diagnosis and treatment of PCa.

6.
J Hepatol ; 71(4): 685-698, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31173811

RESUMO

BACKGROUND & AIMS: CD100 is constitutively expressed on T cells and can be cleaved from the cell surface by matrix metalloproteases (MMPs) to become soluble CD100 (sCD100). Both membrane-bound CD100 (mCD100) and sCD100 have important immune regulatory functions that promote immune cell activation and responses. This study investigated the expression and role of mCD100 and sCD100 in regulating antiviral immune responses during HBV infection. METHODS: mCD100 expression on T cells, sCD100 levels in the serum, and MMP expression in the liver and serum were analysed in patients with chronic HBV (CHB) and in HBV-replicating mice. The ability of sCD100 to mediate antigen-presenting cell maturation, HBV-specific T cell activation, and HBV clearance were analysed in HBV-replicating mice and patients with CHB. RESULTS: Patients with CHB had higher mCD100 expression on T cells and lower serum sCD100 levels compared with healthy controls. Therapeutic sCD100 treatment resulted in the activation of DCs and liver sinusoidal endothelial cells, enhanced HBV-specific CD8 T cell responses, and accelerated HBV clearance, whereas blockade of its receptor CD72 attenuated the intrahepatic anti-HBV CD8 T cell response. Together with MMP9, MMP2 mediated mCD100 shedding from the T cell surface. Patients with CHB had significantly lower serum MMP2 levels, which positively correlated with serum sCD100 levels, compared with healthy controls. Inhibition of MMP2/9 activity resulted in an attenuated anti-HBV T cell response and delayed HBV clearance in mice. CONCLUSIONS: MMP2/9-mediated sCD100 release has an important role in regulating intrahepatic anti-HBV CD8 T cell responses, thus mediating subsequent viral clearance during HBV infection. LAY SUMMARY: Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. The clearance of HBV relies largely on an effective T cell immune response, which usually becomes dysregulated in chronic HBV infection. Our study provides a new mechanism to elucidate HBV persistence and a new target for developing immunotherapy strategies in patients chronically infected with HBV.

7.
BMC Gastroenterol ; 19(1): 65, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046700

RESUMO

BACKGROUND: Pegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial. METHODS: Eligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 µg/kg/wk. 24 weeks or 1.5 µg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA < 2000 IU/mL. RESULTS: The proportions of patients achieving sustained SR among patients who had SR at EOS were high in three treatment groups (61.9, 65.5, 76.5%, respectively, p = 0.46); treatment with PEG-IFN alfa-2b 1.5 µg/kg/wk. 48 weeks had the highest proportion of a sustained CR among patients who had CR at EOS (75.0%, p = 0.05). A considerable number of patients achieved sustained SR (18.2-29.9%) and sustained CR (14.8-18.3%) after EOS despite no further NA treatment. At the LTFU, rates of SR and CR were less than 70.0 and 50.0%, respectively, among all enrolled patients regardless of additional nucleos(t)ide analogs before the LTFU. CONCLUSIONS: PEG IFN alfa-2b therapy had considerable off-treatment sustainability in Chinese HBeAg positive chronic hepatitis B patients with serological and complete responses.


Assuntos
Antivirais/uso terapêutico , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Resposta Viral Sustentada , Adulto , Antivirais/administração & dosagem , China , Feminino , Seguimentos , Hepatite B Crônica/sangue , Humanos , Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Masculino , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Adulto Jovem
8.
Gastroenterol Res Pract ; 2019: 7103915, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863440

RESUMO

Objective: The aim of our study was to investigate the expression of EGFR and PTEN in tissues and measure the serum platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) to evaluate the prognostic factors of patients with epithelioid malignant peritoneal mesothelioma (MPeM). Methods: 33 patients of pathologically diagnosed epithelioid MPeM tissues were analyzed using immunohistochemistry to detect EGFR and PTEN; the PLR and NLR were determined by using a routine blood test. We analyzed the relationships of these markers to age, sex, asbestos exposure, elevated platelet count, ascites, and clinical stage. Results: EGFR and PTEN expressions were positive in 22 (66.67%) and 7 (21.21%) epithelioid MPeM patients, respectively. However, these two markers as well as PLR and NLR were not significantly associated with age, sex, asbestos exposure, elevated platelet counts, ascites, and clinical stage (P > 0.05). The correlation between EGFR and PTEN was negative (r = -0.577, P < 0.001), but the correlation between NLR and PLR was positive (r = 0.456, P = 0.008). The median survival of all patients was 6 months. In univariate analysis, PTEN (P < 0.001), PLR (P = 0.014), and NLR (P = 0.015) affected the overall survival. Multivariate analysis revealed that PTEN and PLR were validated as predictive for overall survival of epithelioid MPeM (HR = 0.070, P = 0.001, and HR = 3.379, P = 0.007, respectively). Conclusion: On the basis of these results, it is suggested that PTEN and PLR are risk factors for the prognosis of epithelioid MPeM, which may be targets for selective therapies and improve the outcomes of patients with epithelioid MPeM.

9.
Antivir Ther ; 24(4): 237-246, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30882363

RESUMO

BACKGROUND: A unique chronic hepatitis B patient was followed over 189 months of nucleoside/nucleotide analogue (NA) therapies with the analysis of multiple drug-resistance HBV mutants. METHODS: Clonal sequencing (≥20 clones/sample) was performed on sera sampled at 41 time points, and the phenotypic features of eight representative mutants were analysed. RESULTS: Lamivudine (LAM)-, adefovir dipivoxil (ADV)-, entecavir (ETV)- and repeat ADV-resistance mutants emerged upon individual sequential NA monotherapy. The efficacy of NA combination rescue therapies ranked as LAM+ADV < ETV+ADV < ETV+ tenofovir disoproxil fumarate (TDF). Specifically, LAM+ADV and ETV+ADV suppressed viral loads to <100 IU/ml for a long period of time, either with or without late stage HBV DNA fluctuations. Furthermore, ETV+TDF suppressed the viral load to <10 IU/ml. During the LAM+ADV and ETV+ADV combination therapies, ETV-resistance mutants dominated at most time points, and multidrug-resistance (MDR) mutants that harboured LAM-, ETV- and ADV-resistance mutations were intermittently detected. Interestingly, the rtA181T-causative sW172stop to sW172non-stop mutation transition was observed at HBV DNA fluctuations. In a phenotypic analysis, two MDR strains had cross-resistance to LAM, ETV and ADV, and a lower susceptibility to TDF (<10-fold decrease compared with the wild-type strain). In contrast, the natural replication capacity was inversely associated with the number of primary resistant mutations which would limit MDR mutant development. CONCLUSIONS: Taken together, viral drug susceptibility, replication capacity, and perhaps immunological adaptation may play coordinated roles in the fitness of drug-resistance mutants. ETV+TDF therapy is the preferred option for treating chronic hepatitis B patients with multiple drug failure.

10.
J Phys Condens Matter ; 31(26): 265404, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-30921778

RESUMO

The pressure-induced phase-transition sequences and structural evolution across the insulator-metal transition (IMT) in multiferroic BiFeO3 still remain unclear. Here we use a combination of high-pressure XRD, XAFS experiment and first principle calculation to investigate the pressure-derived structural transformations and structure-related properties in bulk and nanoscale BiFeO3 up to 55 GPa. A new Imma structure of BiFeO3 has been discovered in the pressure range of 48-52 GPa, which presents ferromagnetic (FM) metallic properties and therefore plays a key role in the IMT. Local structure study reveals that the Bi3+ cation gradually shifts toward the centrosymmetric position in BiO12 cluster during IMT. Besides, the detailed structural information of post-perovskite Cmcm phase has also been determined and thus the complete phase sequence up to 60 GPa is obtained. Our research provides a structural origin of the IMT and a new way to understand the FM release in BiFeO3 system.

11.
Gastroenterology ; 156(8): 2230-2241.e11, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30742832

RESUMO

BACKGROUND & AIMS: We performed a nationwide, retrospective study to determine the incidence and causes of drug-induced liver injury (DILI) in mainland China. METHODS: We collected data on a total of 25,927 confirmed DILI cases, hospitalized from 2012 through 2014 at 308 medical centers in mainland China. We collected demographic, medical history, treatment, laboratory, disease severity, and mortality data from all patients. Investigators at each site were asked to complete causality assessments for each case whose diagnosis at discharge was DILI (n = 29,478) according to the Roussel Uclaf Causality Assessment Method. RESULTS: Most cases of DILI presented with hepatocellular injury (51.39%; 95% confidence interval [CI] 50.76-52.03), followed by mixed injury (28.30%; 95% CI 27.73-28.87) and cholestatic injury (20.31%; 95% CI 19.80-20.82). The leading single classes of implicated drugs were traditional Chinese medicines or herbal and dietary supplements (26.81%) and antituberculosis medications (21.99%). Chronic DILI occurred in 13.00% of the cases and, although 44.40% of the hepatocellular DILI cases fulfilled Hy's Law criteria, only 280 cases (1.08%) progressed to hepatic failure, 2 cases underwent liver transplantation (0.01%), and 102 patients died (0.39%). Among deaths, DILI was judged to have a primary role in 72 (70.59%), a contributory role in 21 (20.59%), and no role in 9 (8.82%). Assuming the proportion of DILI in the entire hospitalized population of China was represented by that observed in the 66 centers where DILI capture was complete, we estimated the annual incidence in the general population to be 23.80 per 100,000 persons (95% CI 20.86-26.74). Only hospitalized patients were included in this analysis, so the true incidence is likely to be higher. CONCLUSIONS: In a retrospective study to determine the incidence and causes of DILI in mainland China, the annual incidence in the general population was estimated to be 23.80 per 100,000 persons; higher than that reported from Western countries. Traditional Chinese medicines, herbal and dietary supplements, and antituberculosis drugs were the leading causes of DILI in mainland China.


Assuntos
Causas de Morte , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Terminal/induzido quimicamente , Falência Hepática Aguda/induzido quimicamente , Sistema de Registros , Doença Aguda , Adulto , Distribuição por Idade , Idoso , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , China/epidemiologia , Doença Crônica , Estudos de Coortes , Intervalos de Confiança , Doença Hepática Terminal/epidemiologia , Doença Hepática Terminal/fisiopatologia , Feminino , Humanos , Incidência , Falência Hepática Aguda/epidemiologia , Falência Hepática Aguda/fisiopatologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Taxa de Sobrevida , Adulto Jovem
12.
Angew Chem Int Ed Engl ; 58(14): 4576-4580, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30729635

RESUMO

We report a new type of MAX phase (M=transition metals, A=main group elements, and X=C/N), Nb3 As2 C, designated as 321 phase. It differs from all the previous Mn+1 AXn phases in that it consists of an alternate stacking of one MX layer and two MA layers in its unit cell, while only one MA layer is allowed in usual MAX phases. The new 321 phase exhibits a bulk modulus of Nb3 As2 C up to 225(3) GPa as determined by high-pressure synchrotron X-ray diffraction, one of the highest values among MAX phases. Isostructural 321 phases V3 As2 C, Nb3 P2 C, and Ta3 P2 C are also found to exist. First-principles calculations reveal the outstanding elastic stiffness in 321 phases. Among all 321 phases, Nb3 P2 C is predicted to have the highest elastic properties. These 321 phases, represented by a chemical formula Mn+1 An X, were added as new members to the MAX family and their other properties deserve future investigations.

13.
Chem Commun (Camb) ; 55(19): 2789-2792, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30758352

RESUMO

Novel rhombic dodecahedral SnS nanocrystals were prepared via a facile one-pot hydrothermal method for the first time, which exhibit a large extinction coefficient of 36.8 L g-1 cm-1 and a high photothermal conversion efficiency of 39.4% under irradiation with a 785 nm laser. Moreover, they show good performance for photothermal therapy of HeLa tumors.


Assuntos
Lasers , Nanopartículas Metálicas/química , Sulfetos/química , Compostos de Estanho/química , Animais , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Nus , Fototerapia , Temperatura Ambiente , Transplante Heterólogo , Neoplasias do Colo do Útero/terapia
14.
Res Gerontol Nurs ; 12(1): 44-55, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30653651

RESUMO

The current study explored whether mutuality and coping predicted and/or mediated the effect of a nurse-led cognitive behavioral intervention (NLCBI) on depressive symptoms of caregivers of persons with dementia. The intervention group (n = 56) received five monthly in-home nurse-led cognitive behavioral sessions and consultation calls after each session. The control group (n = 56) received five monthly short general conversations with the nurse interventionist. Questionnaires on study variables and demographics were collected at baseline, end of intervention, and 2-month follow up. Improved mutuality (ß = -0.75, p = 0.049) and active coping (ß = -2.06, p = 0.0001) and decreased passive coping (ß = 1.43, p = 0.001) were found to predict the reduction of depressive symptoms among caregivers in the NLCBI. However, none of these variables mediated the interventional effect. Regular mental health nursing interventions are suggested to focus on enhancing mutuality and active coping and decreasing passive coping to maintain caregivers' mental health. TARGETS: Caregivers of persons with dementia. INTERVENTION DESCRIPTION: Nurse-led cognitive behavioral sessions and subsequent consultation calls. MECHANISMS OF ACTION: Impacted caregivers' reappraisals, thus improving their active coping skills and mutuality and decreasing their passive coping, which directly reduced their depressive symptoms. OUTCOMES: Mutuality, active coping, and passive coping played a predicting, but not mediating, role in the effect of the NLCBI. [Res Gerontol Nurs. 2019; 12(1):44-55.].


Assuntos
Cuidadores/educação , Terapia Cognitivo-Comportamental/métodos , Aconselhamento/métodos , Demência/enfermagem , Papel do Profissional de Enfermagem , Adaptação Psicológica , Adulto , Idoso , Cuidadores/psicologia , Demência/psicologia , Depressão/prevenção & controle , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Apoio Social , Inquéritos e Questionários
15.
J Adv Nurs ; 75(5): 1018-1028, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30375030

RESUMO

AIMS: This study aimed to describe the status of patient delay and examine related factors affecting patient delay in individuals with haemorrhoids in mainland China, based on theory of planned behaviour and common sense model. BACKGROUND: Studies on patient delay have mainly focused on cancer, tuberculosis and myocardial infarction, but studies on patient delay in individuals with haemorrhoids have yet to be conducted. Compared with other diseases, haemorrhoids are initially considered benign. However, if patients with haemorrhoids seek delayed medical assistance, they pay a large cost for worse symptoms because they fail to seek timely treatments compared with those who receive appropriate treatments at early stages. DESIGN: A cross-sectional study design was used. METHODS: The current study was performed on 306 patients with haemorrhoids from June - October 2017. Data were collected via a self-administered pencil-and-paper survey that consisted of a multi-item questionnaire. Stepwise logistic regression analysis was conducted to explore the factors of patient delay. RESULTS: Middle-aged participants were more than twice more likely to report patient delay than participants in other age groups. A high level of perceived self-efficacy, a high level of illness perceptions and perceived social impact were associated with prolonged delay. CONCLUSION: This study showed that patient delay is common among patients with haemorrhoids in China. The influencing factors of patient delay were middle-aged, illness perceptions, perceived self-efficacy, and perceived social impact.


Assuntos
Terapia Comportamental/métodos , Hemorroidas/diagnóstico , Hemorroidas/terapia , Tempo para o Tratamento/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
16.
J Viral Hepat ; 26(1): 73-82, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30260541

RESUMO

Adaptation of hepatitis C virus (HCV) to CD8+ T cell selection pressure is well described; however, it is unclear if HCV differentially adapts in different populations. Here, we studied HLA class I-associated viral sequence polymorphisms in HCV 1b isolates in a Chinese population and compared viral substitution patterns between Chinese and German populations. We identified three HLA class I-restricted epitopes in HCV NS3 with statistical support for selection pressure and found evidence for differential escape pathways between isolates from China and Germany depending on the HLA class I molecule. The substitution patterns particularly differed in the epitope VTLTHPITK1635-1643 , which was presented by HLA-A*03 as well as HLA-A*11, two alleles with highly different frequencies in the two populations. In Germany, a substitution in position seven of the epitope was the most frequent substitution in the presence of HLA-A*03, functionally associated with immune escape and nearly absent in Chinese isolates. In contrast, the most frequent substitution in China was located at position two of the epitope and became the predominant consensus residue. Moreover, substitutions in position one of the epitope were significantly enriched in HLA-A*11-positive individuals in China and associated with different patterns of CD8+ T cell reactivity. Our study confirms the differential escape pathways selected by HCV that depended on different HLA class I alleles in Chinese and German populations, indicating that HCV differentially adapts to distinct HLA class I alleles in these populations. This result has important implications for vaccine design against highly variable and globally distributed pathogens, which may require matching antigen sequences to geographic regions for T cell-based vaccine strategies.

17.
J Telemed Telecare ; 25(7): 402-413, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29909748

RESUMO

INTRODUCTION: Hypoglycaemia is a clinical syndrome from various causes, which happens when the blood glucose concentration is too low. Many studies show that telemedicine intervention can improve glycemic control and has a positive impact on the management of diabetic patients. The purpose of this study was to evaluate the effect of telemedicine intervention on hypoglycemic event occurrences and results on hemoglobin A1c (HbA1c) and body mass index (BMI). METHODS: We searched the Cochrane Library, PubMed, Web of Science, the EBSCO host, and OVID to identify relevant studies published from January 2006 to December 2017. The work of searching, selecting and assessing risk of bias was administrated by two independent reviewers. The primary outcomes were hypoglycemic event rate and HbA1c; the secondary outcome was BMI. RESULTS: From 1246 articles, we identified 14 eligible RCTs (n = 1324). Compared to usual care, telemedicine was found to reduce the odds of hypoglycaemia (odds ratio (OR) = 0.42; 95% confidence interval (CI) = 0.29-0.59; I2 = 32%; p < 0.00001). We found that the clinical relevance declined in HbA1c level compared to control group (mean difference = -0.28; 95% CI = -0.45 to -0.12; I2 = 53%; p = 0.0005), but that telemedicine had no effect on BMI (mean difference = -0.27; 95% CI = -0.86-0.31; I2 = 40%; p = 0.35). DISCUSSION: Compared to usual care, the use of telemedicine was found to improve HbA1c and reduce the risk of moderate hypoglycaemia in diabetic patients, but without significant difference in BMI.

19.
Front Immunol ; 9: 1495, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30008718

RESUMO

Toll-like receptors (TLRs) play a crucial role in activation of innate immunity, which is essential for inducing effective adaptive immune responses. Our previous studies have shown that toll-like receptor 2 (TLR2) is required to induce effective virus-specific T-cell responses against hepatitis B virus (HBV) in vivo. However, the contribution of TLR2 activation to adaptive immunity and HBV clearance remains to be clarified. In this study, we explored the hydrodynamic injection (HI) mouse models for HBV infection and examined how the TLR2 agonist Pam3CSK (P3C) influences HBV control and modulates HBV-specific T-cell response if applied in vivo. We found that TLR2 activation by P3C injection leads to the rapid but transient production of serum proinflammatory factors interleukin-6 and tumor necrosis factor-α and activation of CD8+ T cells in vivo. Then, the anti-HBV effect and HBV-specific T-cell immunity were investigated by TLR2 activation in the mouse models for persistent or acute HBV infections using HBV plasmids pAAV-HBV1.2 and pSM2, respectively. Both P3C application at early stage and pre-activation promoted HBV clearance, while only TLR2 pre-activation enhanced HBV-specific T-cell response in the liver. In the mouse model for acute HBV infection, P3C application had no significant effect on HBV clearance though P3C significantly enhanced the HBV-specific T-cell response. Collectively, TLR2 pre-activation enhances HBV-specific T-cell responses and accelerates HBV clearance in HI mouse models. Thus, the modulation of host immune status by TLR2 agonists may be explored for immunotherapeutic strategies to control HBV infection.

20.
Clin Immunol ; 195: 8-17, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30036637

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by a novel bunyavirus with high mortality. Immune suppression is thought to be crucial in disease progression. However, data on immune responses during SFTS are scarce. This study aimed to evaluate the changes in CD4 T-cell subsets throughout the entirety of infection and analyse their relationships with disease severity in SFTS patients. In parallel with CD4 T-cell depletion, decreased Th1, Th2 and Treg numbers, but comparable Th17-cell numbers, were observed in deceased patients compared with those in surviving patients. Additionally, increased Th2 and Th17-cell percentages in the residual CD4 T-cell population led to aberrant Th2/Th1 and Th17/Treg ratios, which were positively correlated with disease severity. Collectively, our data indicated that CD4 T-cell deficiency, Th2 and Th17 bias were closely correlated with the severity of SFTS, indicating therapeutic potential of early immune interventions to ameliorate disease severity.


Assuntos
Infecções por Bunyaviridae/imunologia , Phlebovirus/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD4/metabolismo , Progressão da Doença , Feminino , Humanos , Imunossupressão , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Equilíbrio Th1-Th2 , Adulto Jovem
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