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1.
J Viral Hepat ; 27(1): 45-51, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31520460

RESUMO

A simple, pangenotypic and effective treatment regimen for patients with a broad range of chronic hepatitis C virus (HCV) infections remains an unmet medical need. We conducted a phase 2, randomized, open study involving untreated patients with chronic HCV genotypes 1, 2, 3, or 6 infections. Patients without cirrhosis were randomly assigned in a 1:2 ratio to receive capsules of the NS5A inhibitor coblopasvir at a dose of 30 or 60 mg plus tablets of the nucleotide polymerase inhibitor sofosbuvir (400 mg) once daily for 12 weeks. Patients with cirrhosis received 60 mg coblopasvir plus sofosbuvir for 12 weeks. The primary endpoint was the sustained virologic response at 12 weeks after the end of therapy (SVR12). Of the 110 patients who were enrolled in the study, 59 were male, 62.7% had HCV genotype 1, 24.5% had genotype 2, 6.4% had genotype 3, and 6.4% had genotype 6. The average age was 45.5 years. A total of 10.9% of patients had compensated cirrhosis. The rate of SVR12 was 98.2% in the intention-to-treat (ITT). One genotype 6 patient with cirrhosis experienced virologic relapse. One genotype 2 patient without cirrhosis failed to complete the follow-up and quit the study. Serious adverse events (SAEs) were reported in 2 patients and were not related to coblopasvir and sofosbuvir. Most adverse events (AEs) did not require treatment. Coblopasvir plus sofosbuvir taken once daily for 12 weeks provided high rates of sustained virologic response (SVR) and had a good safety profile among patients with HCV genotypes 1, 2, 3, or 6 infections, including those with compensated cirrhosis.

2.
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.

3.
J Clin Transl Hepatol ; 7(3): 221-225, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608213

RESUMO

Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis. Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 µg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate. Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9-99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident. Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated. Trial Registration Clinical-Trials.gov Identifier: NCT03020082.

4.
Arch Virol ; 164(11): 2683-2690, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31428915

RESUMO

Current antiviral therapies against hepatitis B virus (HBV) infections, such as treatment with nucleos(t)ide analogs (NAs) and interferon alpha, can significantly lower HBV DNA titers, eventually to undetectable levels. However, it is still difficult to completely eliminate the stable template of HBV, the covalently closed circular DNA (cccDNA), and this contributes to viral rebound when treatment is discontinued. HBV pregenomic RNA (pgRNA), which was recently found to be present in the enveloped mature HBV viral particle in blood, is tentatively regarded, with still accumulating clinical evidence, as a novel bona fide virological marker reflecting the amount and status of cccDNA when serum HBV DNA becomes undetectable. HBV pgRNA and DNA share almost identical sequences, and it is therefore difficult to differentiate pgRNA from viral DNA using normal PCR methods. To exclude interference from viral DNA, methods for measuring pgRNA usually require a selective DNA degradation step, which is complicated and time-consuming and also compromises the accuracy of detection. In this study, we developed a simplified quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay with improved accuracy achieved by probing the polyA tail of pgRNA. Using clinical serum samples, we observed that not all patients share the same 3' sequence, suggesting slight differences between HBV strains in the way they end transcription. We then designed and evaluated a universal primer and probe set for distinguishing HBV pgRNA from HBV DNA. Our results demonstrated that a one-step qRT-PCR assay could selectively amplify HBV pgRNA from a mixture of HBV RNA and DNA, which is valuable for clinical applications.


Assuntos
Vírus da Hepatite B/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , DNA Viral/análise , DNA Viral/genética , Hepatite B/virologia , Humanos , RNA Viral/análise , RNA Viral/genética
5.
J Viral Hepat ; 26 Suppl 1: 77-84, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31380586

RESUMO

Chronic hepatitis B virus (HBV) infection (CHB) in children remains a public health challenge despite significant success in programme is established to prevent mother-to-child transmission. In particular, CHB in Chinese children are mostly acquired through vertical transmission, which differs from the common infection route reported in other countries and regions. This situation has resulted in a high endemic prevalence of CHB in Chinese adults. Thus, successful treatment of children with CHB will prevent the development of advanced liver diseases in late adulthood. However, there is still no consensus on the clinical guideline to treat paediatric CHB. In this study, we evaluated the potential of interferon alpha (IFNa) treatment for Chinese children with CHB. A total of 41 patients with CHB aged 3-17 years were enrolled in this retrospective study: 21 patients were treated with pegylated (PEG)-IFNa and 20 patients without treatment served as the control group. The rates of HBV DNA suppression, hepatitis B e antigen (HBeAg) clearance and hepatitis B surface antigen (HBsAg) clearance were significantly higher in the PEG-IFNa treatment group than in the control group (P < 0.05 at 48 weeks). Unexpectedly, PEG-IFNa treatment achieved a high rate of HBsAb production, far exceeding the clinical outcome in documented PEG-IFNa-treated CHB adults. Further analysis revealed that younger children (3-6 years old) were more responsive to PEG-IFNa treatment with respect to achieving a protective level of HBsAb in a short treatment cycle than adolescents (10-17 years old). Overall, these results indicate that the immune system of children might have a preserved PEG-IFNa-mediated mechanism to completely control HBV, which can help to design new strategies to treat CHB patients.

6.
J Exp Med ; 215(8): 2157-2174, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-30049704

RESUMO

Group 2 innate lymphoid cells (ILC2s) are emerging as key players in the pathogenesis of allergic airway inflammation. The mechanisms regulating ILC2, however, are not fully understood. Here, we found that ICAM-1 is required for the development and function of ILC2. ICAM-1-deficient (ICAM-1-/- ) mice displayed significantly lower levels of ILC2s in the bone marrow and peripheral tissues than wild-type controls. CLP transfer and in vitro culture assays revealed that the regulation of ILC2 by ICAM-1 is cell intrinsic. Furthermore, ILC2s from ICAM-1-/- mice were functionally impaired, as indicated by the diminished production of type-2 cytokines in response to IL-33 challenge. The reduction in lung ILC2s caused a clear remission of airway inflammation in ICAM-1-/- mice after administration of papain or Alternaria alternata. We further demonstrate that ILC2 defects caused by ICAM-1 deficiency are due to ERK signaling-dependent down-regulation of GATA3 protein. Collectively, these observations identify ICAM-1 as a novel regulator of ILC2.


Assuntos
Imunidade Inata , Molécula 1 de Adesão Intercelular/metabolismo , Linfócitos/metabolismo , Alternaria/fisiologia , Animais , Fator de Transcrição GATA3/metabolismo , Humanos , Imunidade Inata/efeitos dos fármacos , Interleucina-33/farmacologia , Antígeno-1 Associado à Função Linfocitária/metabolismo , Linfócitos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Pneumonia/imunologia , Pneumonia/microbiologia , Pneumonia/patologia , Ligação Proteica/efeitos dos fármacos
7.
Clin Infect Dis ; 66(1): 29-35, 2018 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-29020289

RESUMO

Background: Human pegivirus type 2 (HPgV-2) is a novel blood-borne human pegivirus that mainly infects hepatitis C virus (HCV)-infected subjects. We have investigated the prevalence of HPgV-2 in China, its association with HCV and human immunodeficiency virus type 1 (HIV-1), and the impact on HCV viral load and liver damage. Methods: A cross-sectional study was conducted with both blood donors and HCV- and HIV-1-infected patients in Guangzhou, China. All subjects were screened for anti-HPgV-2 and HPgV-2 RNA. Demographic and clinical information were obtained from electronic medical records. Results: We tested 8198 serum or plasma samples. Only 0.15% (6/4017) of healthy blood donors were positive for anti-HPgV-2 and negative for HPgV-2 RNA. No HPgV-2 viremia was detected in hepatitis B virus- or HIV-1-monoinfected individuals. The relatively high frequency of HPgV-2 infection was observed in 1.23% (30/2440) and 0.29% (7/2440) of HCV-infected persons by serological assay and reverse-transcription polymerase chain reaction, respectively. Furthermore, anti-HPgV-2 and HPgV-2 RNA were detected in 8.91% (18/202) and 3.47% (7/202), respectively, of HCV/HIV-1-coinfected subjects. HPgV-2 persistent infection was documented in about 30% of anti-HPgV-2-positive individuals. In addition, HPgV-2 infection may not affect HCV-related liver injury and HCV viral load. Conclusions: Our results indicate the rarity of HPgV-2 infection in the general population and tight association with HCV, in particular with HCV/HIV-1 coinfection. HPgV-2 appears not to worsen HCV-related liver damage. Our study provides new findings about the association of HPgV-2 and HCV/HIV-1 and the impact of HPgV-2 infection on HCV replication and pathogenesis.


Assuntos
Coinfecção/virologia , Flaviviridae/classificação , Flaviviridae/isolamento & purificação , Infecções por HIV/complicações , Hepatite C/complicações , Adulto , Doadores de Sangue , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Viral/sangue , Carga Viral
8.
PLoS One ; 10(10): e0140853, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26509605

RESUMO

OBJECTIVES: The optimal treatment of hepatitis C virus (HCV) genotype 6 is unclear owing to its limited geographic distribution. Because of a high predictive value of rapid virological response (RVR) for sustained virological response (SVR), we conducted an open-label randomized controlled trial to compare 24- and 48-week peginterferon/ribavirin combination therapy for patients with HCV genotype 6 in Southern China who achieved an RVR. METHODS AND FINDINGS: Treatment-naive, non-cirrhotic patients with chronic hepatitis C genotype 6 were treated with pegylated interferon α-2a (180 µg/week) and ribavirin (800-1,200 mg, according to weight) for 4 weeks. Patients who achieved an RVR, which was defined as HCV RNA negativity at week 4 (<50 IU), were randomized to receive either an additional 20 or 44 weeks of treatment (24- and 48-week treatment groups, respectively). The primary outcome measure was SVR. From January 2011 to June 2014, 152(152/210, 72.4%) patients with HCV genotype 6a and RVR were randomized 1:1 to the 24- or 48-week treatment group. The SVR rates in the 24- and 48-week groups in the intention-to-treat analysis were 90.8% (69/76) and 88.2% (67/76), respectively; those in the per-protocol analysis were 95.7% (67/70) and 97.0% (64/66), respectively. More patients in the 48-week group had anemia (46.1% vs. 28.9%, P = 0.03), but other adverse events were comparable between the groups. The limitation of the present study was that only patients from Southern China were enrolled which may inhibit the extensive application of the findings. CONCLUSION: Twenty-four weeks of peginterferon/ribavirin combination therapy was non-inferior to 48 weeks in patients with HCV genotype 6a in Southern China who achieved an RVR. TRIAL REGISTRATION: ClinicalTrials.gov NCT01263860.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepacivirus/patogenicidade , Ribavirina/uso terapêutico , Adolescente , Adulto , Idoso , China , Feminino , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Humanos , Interferon-alfa , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , RNA Viral/genética , Proteínas Recombinantes , Resultado do Tratamento , Adulto Jovem
9.
PLoS One ; 10(7): e0133800, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26193702

RESUMO

Suppressor of cytokine signaling 1 (SOCS1) has long been thought to block type I interferon signaling. However, IFN-λ, a type III IFN with limited receptor expression in hepatic cells, efficiently inhibits HCV (Hepatitis C virus) replication in vivo with potentially less side effects than IFN-α. Previous studies demonstrated that type I and type III activated Janus kinase/signal transducer and activator of transcription (Jak/STAT) signaling pathway differently, with delayed but prolonged activation by IFN-λ stimulation compared to IFNα/ß. However, the molecular mechanisms underlying this observation is not well understood. Here, we found that there are distinct differences in SOCS1 expression patterns in Huh-7.5.1 cells following stimulation with IFN-α and IFN-λ. IFN-λ induced a faster but shorter expression of SOCS1. Furthermore, we confirmed that SOCS1 over-expression abrogates anti-HCV effect of both IFN-α and IFN-λ, leading to increased HCV RNA replication in both HCV replicon cells and JFH1 HCV culture system. In line with this, SOCS1 over-expression inhibited STAT1 phosphorylation, attenuated IFN-stimulated response elements (ISRE) reporter activity, and blocked IFN-stimulated genes (ISGs) expression. Finally, we measured SOCS1 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) with or without IFN-α treatment from 48 chronic hepatitis C patients and we found the baseline SOCS1 expression levels are higher in treatment non-responders than in responders before IFN-α treatment. Taken together, SOCS1 acts as a suppressor for both type I and type III IFNs and is negatively associated with sustained virological response (SVR) to IFN-based therapy in patients with HCV. More importantly, faster but shorter induction of SOCS1 by IFN-λ may contribute to delayed but prolonged activation of IFN signaling and ISG expression kinetics by type III IFN.


Assuntos
Interferons/farmacologia , Janus Quinases/metabolismo , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Antivirais/farmacologia , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virologia , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepacivirus/fisiologia , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Interferon-alfa/farmacologia , Interleucinas/farmacologia , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/genética , Fatores de Tempo
10.
Mediators Inflamm ; 2015: 508989, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26060358

RESUMO

Calcitriol, the bioactive metabolite of vitamin D, was reported to inhibit HCV production in a synergistic fashion with interferon, a treatment in vitro. Our previous study established that miR-130a inhibits HCV replication by restoring the host innate immune response. We aimed to determine whether there is additive inhibitory effect of calcitriol and miR-130a on HCV replication. Here we showed that calcitriol potentiates the anti-HCV effect of miR-130a in both Con1b replicon and J6/JFH1 culture systems. Intriguingly, this potentiating effect of calcitriol on miR-130a was not through upregulating the expression of cellular miR-130a or through increasing the miR-130a-mediated IFNα/ß production. All these findings may contribute to the development of novel anti-HCV therapeutic strategies although the antiviral mechanism needs to be further investigated.


Assuntos
Hepacivirus/efeitos dos fármacos , Hepacivirus/fisiologia , Interferon Tipo I/metabolismo , Vitamina D/metabolismo , Calcitriol/metabolismo , Calcitriol/farmacologia , Linhagem Celular , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
11.
Artigo em Chinês | MEDLINE | ID: mdl-22919746

RESUMO

OBJECTIVE: To investigate the hepatitis B virus (HBV) mutation in the Enhancer I (HBV Enh I)/X-promoter and to analysis the relationship between chronic HBV-related disease spectrum. METHODS: 275 patients were enrolled in this study, including 100 cases of chronic hepatitis B (CHB), 74 cases of liver cirrhosis (LC), 101 cases of hepatocellular carcinoma (HCC), grouping by different HBV genotypes, using semi-nested PCR amplification of HBV Enh I/X-promoter and sequencing DNA, the mutations were determined by alignment to HBV reference sequence, the data was compared by chi2 test and analyzed by multivariate logistic regression. RESULTS: (1) Genotyping results: 61.48% (158/257) were infected with HBV genotype B, including 70 cases of CHB, 36 cases of LC and 52 cases of HCC; 38.52% (117/257) were infected with HBV genotype C, including 30 cases of CHB, 38 cases of LC and 49 cases of HCC. (2) In the patients were infected with HBV genotype B, A1123Y mutation in LC was significantly higher than in CHB (30.56% vs. 8.58%, chi2 = 8.533, P = 0.005, A = 4.693, 95% CI [1.567-14.056]), HCC was significantly higher than in CHB (28.85% vs. 8.58%, chi2 = 8.607, P = 0.003, A = 4.324,95% CI [1.544-2.109]); A1317G mutation in HCC was significantly higher than in CHB (30.77% vs. 7.14%, chi2 = 11.687, P = 0.001, A = 5.778, 95% CI [1.955-17.076]). In the patients were infected with HBV genotype C, T1323C mutation in HCC was significantly higher than in CHB (30.61% vs. 6.67%, chi2 = 6.318, P = 0.12, A = 6.176, 95% CI [1.301-29.331]). (3) Multivariate regression analyses showed that A1317G (OR = 5.706, 95% CI [1.770-18.837], P = 0.004) and T1323C (A = 5.810, 95% CI [1.114-30.306], P = 0.037) mutation were risk factors for HCC. CONCLUSION: HBV Enh I/X-promoter mutations were associated with the development of LC and HCC, the mutations can help to predict the occurrence of LC and HCC.


Assuntos
Elementos Facilitadores Genéticos , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Mutação , Regiões Promotoras Genéticas , Adulto , Idoso , Feminino , Genótipo , Vírus da Hepatite B/classificação , Humanos , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade
13.
Zhonghua Gan Zang Bing Za Zhi ; 19(9): 678-82, 2011 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-22152383

RESUMO

OBJECTIVE: To study the copy numbers and mRNA expression levels of the Programmed Death-1 gene in chronic hepatitis B patients and to analyze the differences of the copy numbers and mRNA expression levels of the gene in patients with different clinical outcomes. METHODS: Real time PCR was adopted to detect the PD-1 gene copy numbers and their mRNA expressions in peripheral blood mononuclear cells (PBMCs) from 27 samples from healthy donors in Control group, 31 samples from chronic asymptomatic HBV carriers (ASC, n=31), 19 samples from chronic severe hepatitis B patients (CSH, n=19) and 29 samples from Primary hepatitis B Virus-related hepatocarcinoma (PHC, n=29). The differences and relationship of copy numbers and their mRNA expression levels among those groups were compared and analyzed by adopting Chi-square test and Rank sum test. RESULTS: PD-1 gene copy number deviated from 0 copy to 3 copies among all the 106 samples. In control group, ASC group, CSH group and PHC group, the percentages of cases of haploid (single) were 37.0%, 35.5%, 26.3% and 6.9%, respectively, the percentages of cases of diploid (double) were 55.5%, 58.0%, 63.2% and 82.8%, respectively, and the percentages of cases of triploid (triple) were 3.7%, 6.5%, 10.5% and 10.3%, respectively. The percentage of cases of polyploid (diploid and triploid) in control group, ASC group, CSH group and PHC group were 59.3%, 64.5%, 73.7% and 93.1%, respectively. The different distribution of PD-1 gene copy number of polyploid was significant in total samples (x2=9.583, P<0.05). Compared with Control Group and ASC group, the percentage of cases of polyploid in PHC group was lower with the x2 equals to 8.985 and 7.215 respectively and both with P less than 0.05. The difference between the two groups was statistically significant. The mean PD-1 gene copy numbers for these four groups were 1.59+/-0.63, 1.70+/-0.52, 1.84+/-0.60 and 2.00+/-0.37 while the median were 0.002 54, 0.002 72, 0.002 55 and 0.001 33 respectively. Except the control group, there was a uptrend in the other three groups while PD-1 gene mRNA expression presented a downtrend. The mean of PD-1 gene copy numbers of 2 and their mRNA expression levels were 19.59, 32.57 and 33.22 for PHC, CSH and ASC groups among which PHC group had the lowest value, there was significant differences found in the comparison with F=5.395 and P<0.05. CONCLUSION: PD-1 gene copy numbers and their mRNA expression levels were different in chronic HBV infected patients with different transformation. It is valuable to follow up the patients with more than 1 copy number of PD-1 gene in long term.


Assuntos
Dosagem de Genes , Hepatite B Crônica/genética , Receptor de Morte Celular Programada 1/genética , Adulto , Estudos de Casos e Controles , Feminino , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Adulto Jovem
14.
Ying Yong Sheng Tai Xue Bao ; 18(12): 2807-13, 2007 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-18333459

RESUMO

Based on the field survey and the interpretation and analysis of satellite images about the population expansion patterns of Spartina alterniflora and Phragmites australis at Jiuduansha shoals in 1997-2004, and combined with 3S techniques, a cellular automata (CA) model was built to simulate the population dynamics of plants adaptable to salt marsh. The results showed that the model could well simulate the population expansion pattern and trend of S. alterniflora and P. australis at Jiuduansha, and strongly supported the hypothesis of space pre-emption and range expansion with simple advancing wave fronts of these two species. The native species P. australis shared the same niche with the exotic species S. alterniflora, but the range expansion rate of S. alterniflora was 2-4 times faster than that of P. australis. With the accretion of the Jiuduansha shoals, a rapid range expansion of S. alterniflora was predicted to last for a long period in the future. The CA model built in this study could gain valuable insights into the relationships between population expansion pattern and its ecological processes of exotic plant species, and was of significance for wetland biodiversity conservation and resources management.


Assuntos
Adaptação Fisiológica , Modelos Biológicos , Poaceae/crescimento & desenvolvimento , Biodiversidade , China , Ecossistema , Poaceae/classificação , Poaceae/fisiologia , Dinâmica Populacional
15.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 17(6): 332-4, 2005 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-15970094

RESUMO

OBJECTIVE: To analyze the laboratory characteristics of patients with sporadic severe acute respiratory syndrome (SARS) in China. METHODS: The laboratory findings of the 4 cases with SARS occurring in Guangzhou, People's Republic of China, in 2004 were analyzed and compared with that during epidemic. RESULTS: Leukopenia and lymphocytopenia were seen in all the patients. Two patients had slightly decreased peripheral blood T lymphocyte count. Alanine aminotransferase (ALT) and aspartate transaminase (AST) levels increased slightly in 3 patients. No hypoxemia was seen in all the patients. Both SARS-IgM and IgG sero-conversion occurred earlier in all the patients with the titer increased more than 4-fold shortly. Neutralization test was positive in all the patients. SARS coronary virus (SARS-CoV) RNA was detected by polymerase chain reaction (PCR) in pharyngeal swabs only in 1 patient. CONCLUSION: The 4 sporadic SARS patients in 2004 have milder manifestations, shorter course of disease with no complications during an epidemic, compared with patients seen previously. The change in laboratory findings is less than that, which might be attributable to milder virulence of the SARS-CoV. The antibody appears earlier in these patients. The SARS-CoV is eliminated rapidly.


Assuntos
Síndrome Respiratória Aguda Grave/epidemiologia , China/epidemiologia , Feminino , Humanos , Masculino , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/sangue
16.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 16(5): 267-70, 2004 May.
Artigo em Chinês | MEDLINE | ID: mdl-15132787

RESUMO

OBJECTIVE: To study the changes in liver function and histopathology, and investigate the underlying mechanism and clinical significance of damage of liver in patients with severe acute respiratory syndrome (SARS). METHODS: According the clinical diagnostic standard of atypical pneumonia of Ministry of Health P. R. China, liver function was assessed in 110 SARS patients admitted from February 2003 to June 2003. Of them 8 SARS patients died, and the livers were pathologically examined, and their liver function parameters were compared with that of the 35 healthy controls. RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBil) of patients with SARS were higher than those of controls, they were (91.61+/-50.53) U/L vs. (32.91+/-10.56) U/L, (78.68+/-33.32) U/L vs. (29.43+/-8.89) U/L, (429.95+/-188.94) U/L vs. (200.83+/-44.86) U/L, (11.67+/-4.26) micromol/L vs. (8.44+/-3.86) micromol/L, all P<0.001. Albumin (ALB) and pro-albumin (PAB) of patients with SARS were lower than those of controls, they were (34.40+/-5.13) g/L vs. (42.09+/-6.79) g/L, (0.20+/-0.06) g/L vs. (0.34+/-0.05) g/L, both P<0.001. Direct reaction bilirubin (DBil), total bile acid (TBA), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) showed no marked difference between SARS patients and controls, all P>0.05. Non-specific inflammation in the liver was observed in pathological examination in 4 cases. ALT, AST, GGT and LDH were always 4 to 9 times of normal. The ratio of abnormality of ALT, AST and PAB were more than 80.0 percent, the ratio of abnormality of ALB was 42.7 percent, and less than 30.0 percent for other indexes. The average of LDH, ALT, and AST of dead patients were higher than those of the survivors. Histopathology of liver was non-specific hepatitis. CONCLUSION: The patients with SARS are prone to have mild non-specific hepatitis. It seldom causes the typical symptoms of hepatitis and it is easy to be ignored in clinic.


Assuntos
Fígado/patologia , Síndrome Respiratória Aguda Grave/complicações , Adulto , Idoso , Alanina Transaminase/sangue , Albuminas/análise , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Fígado/fisiopatologia , Hepatopatias/sangue , Hepatopatias/etiologia , Hepatopatias/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade
17.
Zhonghua Nei Ke Za Zhi ; 42(7): 458-60, 2003 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-12921602

RESUMO

OBJECTIVE: To explore the myocardiac injury in patients with severe acute respiratory syndrome (SARS) and its clinical significance. METHODS: 37 SARS patients fulfilled the Guangdong provincial diagnostic criteria for infectious atypical pneumonia and 35 health controls were investigated. The serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), troponin I (TnI), creatine kinase-MB (CK-MB) and myoglobin (MYO) were measured. RESULTS: CK, LDH and AST levels in patients were higher than those of control group (P < 0.01); furthermore, among patients the levels were higher in fatal cases than in survivors. The positive rates of TnI, CK-MB and MYO in patients were higher than those in controls (P < 0.05). CONCLUSION: The patients with SARS are subject to complicating myocardiac injury. Therefore, careful monitoring of the myocardiac enzyme profiles is of great importance in reducing the complications and mortality in patients with SARS.


Assuntos
Cardiomiopatias/diagnóstico , Síndrome Respiratória Aguda Grave/complicações , Adolescente , Adulto , Idoso , Aspartato Aminotransferases/sangue , Cardiomiopatias/etiologia , Creatina Quinase/sangue , Creatina Quinase Forma MB , Feminino , Humanos , Isoenzimas/sangue , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Mioglobina/sangue , Troponina I/sangue
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