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1.
Hepatol Int ; 15(6): 1402-1412, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34850325

RESUMO

BACKGROUND & AIMS: Immunotherapy with hepatitis B virus (HBV)-specific TCR redirected T (HBV-TCR-T) cells in HBV-related hepatocellular carcinoma (HBV-HCC) patients after liver transplantation was reported to be safe and had potential therapeutic efficacy. We aim to investigate the safety of HBV-TCR-T-cell immunotherapy in advanced HBV-HCC patients who had not met the criteria for liver transplantation. METHODS: We enrolled eight patients with advanced HBV-HCC and adoptively transferred short-lived autologous T cells expressing HBV-specific TCR to perform an open-label, phase 1 dose-escalation study (NCT03899415). The primary endpoint was to evaluate the safety of HBV-TCR-T-cell therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03) during the dose-escalation process. The secondary endpoint was to assess the efficacy of HBV-TCR-T-cell therapy by evaluating the anti-tumor responses using RECIST criteria (version 1.1) and the overall survival. RESULTS: Adverse events were observed in two participants among the 8 patients enrolled. Only one patient experienced a Grade 3 liver-related adverse event after receiving a dose of 1 × 105 HBV-TCR-T cells/kg, then normalized without interventions with immunosuppressive agents. Among the patients, one achieved a partial response lasting for 27.7 months. Importantly, most of the patients exhibited a reduction or stabilization of circulating HBsAg and HBV DNA levels after HBV-TCR-T-cell infusion, indicating the on-target effects. CONCLUSIONS: The adoptive transfer of HBV-TCR-T cells into advanced HBV-HCC patients were generally safe and well-tolerated. Observations of clinical efficacy support the continued development and eventual application of this treatment strategy in patients with advanced HBV-related HCC. CLINICAL TRIALS REGISTRATION: This study was registered at ClinicalTrials.gov (NCT03899415).

2.
EBioMedicine ; 75: 103789, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34963099

RESUMO

BACKGROUND: The long-term consequences of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment for COVID-19 patients are yet to be reported. This study assessed the 1-year outcomes in patients with severe COVID-19, who were recruited in our previous UC-MSC clinical trial. METHODS: In this prospective, longitudinal, cohort study, 100 patients enrolled in our phase 2 trial were prospectively followed up at 3-month intervals for 1 year to evaluate the long-term safety and effectiveness of UC-MSC treatment. The primary endpoint was an altered proportion of whole-lung lesion volumes measured by high-resolution CT. Other imaging outcomes, 6 min walking distance (6-MWD), lung function, plasma biomarkers, and adverse events were also recorded and analyzed. This trial was registered with ClinicalTrials.gov (NCT04288102). FINDINGS: MSC administration improved in whole-lung lesion volume compared with the placebo with a difference of -10.8% (95% CI: -20.7%, -1.5%, p = 0.030) on day 10. MSC also reduced the proportion of solid component lesion volume compared with the placebo at each follow-up point. More interestingly, 17.9% (10/56) of patients in the MSC group had normal CT images at month 12, but none in the placebo group (p = 0.013). The incidence of symptoms was lower in the MSC group than in the placebo group at each follow-up time. Neutralizing antibodies were all positive, with a similar median inhibition rate (61.6% vs. 67.6%) in both groups at month 12. No difference in adverse events at the 1-year follow-up and tumor markers at month 12 were observed between the two groups. INTERPRETATION: UC-MSC administration achieves a long-term benefit in the recovery of lung lesions and symptoms in COVID-19 patients. FUNDING: The National Key R&D Program of China, the Innovation Groups of the National Natural Science Foundation of China, and the National Science and Technology Major Project.

3.
Hepatol Int ; 15(6): 1431-1441, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34843069

RESUMO

BACKGROUND: Mesenchymal stem cell (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC); however, whether the medication can improve outcome of these patients is poorly understood. METHODS: This prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n = 111) and umbilical cord-derived MSC (UC-MSC)-treated group (n = 108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survival rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated. RESULTS: During the follow-up check period from 13 to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group. CONCLUSIONS: Therapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with HBV-related DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease.

4.
5.
Signal Transduct Target Ther ; 6(1): 58, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568628

RESUMO

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.


Assuntos
COVID-19/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , SARS-CoV-2 , Cordão Umbilical , Idoso , Aloenxertos , COVID-19/mortalidade , COVID-19/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Nat Immunol ; 21(9): 1107-1118, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32788748

RESUMO

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Interferon Tipo I/metabolismo , Pneumonia Viral/imunologia , Receptores Imunológicos/metabolismo , Adolescente , Adulto , Idoso , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/genética , Antígenos de Diferenciação de Linfócitos T/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , COVID-19 , Estudos de Coortes , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Humanos , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , RNA-Seq , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , SARS-CoV-2 , Índice de Gravidade de Doença , Análise de Célula Única
7.
Cell Metab ; 32(2): 188-202.e5, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32610096

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. Herein, we utilized a combination of targeted and untargeted tandem mass spectrometry to analyze the plasma lipidome and metabolome in mild, moderate, and severe COVID-19 patients and healthy controls. A panel of 10 plasma metabolites effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma lipidome of COVID-19 resembled that of monosialodihexosyl ganglioside (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s, and reduced diacylglycerols (DAGs). Systems evaluation of metabolic dysregulation in COVID-19 was performed using multiscale embedded differential correlation network analyses. Using exosomes isolated from the same cohort, we demonstrated that exosomes of COVID-19 patients with elevating disease severity were increasingly enriched in GM3s. Our work suggests that GM3-enriched exosomes may partake in pathological processes related to COVID-19 pathogenesis and presents the largest repository on the plasma lipidome and metabolome distinct to COVID-19.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Exossomos/metabolismo , Gangliosídeo G(M3)/sangue , Gangliosídeos/sangue , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Adulto , Idoso , Betacoronavirus , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , COVID-19 , Diglicerídeos/sangue , Feminino , Humanos , Masculino , Metaboloma/fisiologia , Metabolômica/métodos , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Esfingomielinas/sangue , Espectrometria de Massas em Tandem , Adulto Jovem
8.
BMC Infect Dis ; 18(1): 253, 2018 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-29866104

RESUMO

BACKGROUND: Spontaneous bacterial peritonitis (SBP) and bacterascites (BA) represent frequent and serious complications in cirrhosis patients with ascites. However, few detailed data are available regarding the clinical and bacteriological feature of SBP or BA patients in China. METHODS: We retrospectively analyzed bacteriological and clinical characteristics of patients with SBP and BA at Beijing 302 Hospital in China from January 2012 to December 2015. RESULTS: A total of 600 patients with SBP (n = 408) or BA (n = 192) were enrolled. Patients with BA appeared to have a less severe clinical manifestation and lower mortality rate than patients with SBP. Gram-negative bacteria formed the majority of pathogens in SBP (73.9%) and BA (55.8%) cases. Higher ascitic fluid polymorphonuclear leucocytes (PMN) count and hepatocellular carcinoma were independent risk factors for BA episode progressing to SBP. The concentration of blood urea nitrogen (BUN) was independent risk factor for 30-day mortality of BA patients. For patients with SBP, the independent risk factors for 30-day mortality were age, Model for End-Stage Liver Disease (MELD) score, septic shock and hepatocellular carcinoma. Patients with third-generation cephalosporin or carbapenems resistant infection had a significantly lower survival probability. There were significant differences in clinical characteristics and outcome among the major bacteria. Multivariate analysis showed that patients infected with Klebsiella spp. had higher hazard ratio of 30-day mortality. CONCLUSION: Our study reported the bacteriological and clinical characteristics of patients with SBP and BA. Higher ascitic fluid PMN count and hepatocellular carcinoma were found to be independent risk factors for BA episode progressed to SBP. Outcome of ascitic fluid infection in patients with cirrhosis was influenced by the type of bacteria and antimicrobial susceptibility.


Assuntos
Ascite/microbiologia , Infecções Bacterianas/etiologia , Peritonite/etiologia , Adulto , Idoso , Ascite/tratamento farmacológico , Ascite/etiologia , Ascite/mortalidade , Líquido Ascítico/microbiologia , Líquido Ascítico/patologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/mortalidade , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/microbiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/microbiologia , Masculino , Pessoa de Meia-Idade , Peritonite/tratamento farmacológico , Peritonite/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
9.
Microbiol Immunol ; 61(6): 239-246, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28500746

RESUMO

To date, there have been no reports characterizing HIV-1 in the semen of Chinese men who have sex with men (MSM) with early infection. In this study, genetic diversity and viral load of HIV-1 in the seminal compartments and blood of Chinese MSM with early HIV-1 infection were examined. Viral load and genetic diversity of HIV-1 in paired samples of semen and blood were analyzed in seven MSM with early HIV-1 infection. HIV-1 RNA and DNA were quantitated by real-time PCR assays. Through sequencing the C2-V5 region of the HIV-1 env gene, the HIV-1 genotype and genetic diversity based on V3 loop amino acid sequences were determined by using Geno2pheno and PSSM programs co-receptor usage. It was found that there was more HIV-1 RNA in seminal plasma than in blood plasma and total, and more 2-LTR circular and integrated HIV-1 DNA in seminal cells than in peripheral blood mononuclear cells from all seven patients with early HIV-infection. There was also greater HIV-1 genetic diversity in seminal than in blood compartments. HIV-1 in plasma displayed higher genetic diversity than in cells from the blood and semen. In addition, V3 loop central motifs, which present some key neutralizing antibody epitopes, varied between blood and semen. Thus, virological characteristics in semen may be more representative when evaluating risk of transmission in persons with early HIV infection.


Assuntos
Variação Genética , Infecções por HIV/sangue , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/genética , Homossexualidade Masculina , Sêmen/virologia , Carga Viral , Adolescente , Adulto , Motivos de Aminoácidos , Sequência de Aminoácidos , Anticorpos Neutralizantes , Anticorpos Antivirais , Contagem de Linfócito CD4 , DNA Viral/análise , Vetores Genéticos , Genótipo , Proteína gp120 do Envelope de HIV , HIV-1/classificação , Humanos , Leucócitos Mononucleares/virologia , Masculino , Fragmentos de Peptídeos , Filogenia , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real , Doenças Sexualmente Transmissíveis/sangue , Doenças Sexualmente Transmissíveis/virologia , Sequências Repetidas Terminais/genética , Adulto Jovem , Produtos do Gene env do Vírus da Imunodeficiência Humana/classificação , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
10.
Plant Mol Biol ; 94(1-2): 97-107, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28321650

RESUMO

KEY MESSAGE: This research is the first to demonstrate that OsSAUR45 is involved in plant growth though affecting auxin synthesis and transport by repressing OsYUCCA and OsPIN gene expression in rice. Small auxin-up RNAs (SAURs) comprise a large multigene family and are rapidly activated as part of the primary auxin response in plants. However, little is known about the role of SAURs in plant growth and development, especially in monocots. Here, we report the biological function of OsSAUR45 in the model plant rice (Oryza sativa). OsSAUR45 is expressed in a tissue-specific pattern and is localized to the cytoplasm. Rice lines overexpressing OsSAUR45 displayed pleiotropic developmental defects including reduced plant height and primary root length, fewer adventitious roots, narrower leaves, and reduced seed setting. Auxin levels and transport were reduced in the OsSAUR45 overexpression lines, potentially because of decreased expression of Flavin-binding monooxygenase family proteins (OsYUCCAs) and PIN-FORMED family proteins (OsPINs). Exogenous auxin application rapidly induced OsSAUR45 expression and partially restored the phenotype of rice lines overexpressing OsSAUR45. These results demonstrate that OsSAUR45 is involved in plant growth by affecting auxin synthesis and transport through the repression of OsYUCCA and OsPIN gene expression in rice.


Assuntos
Regulação da Expressão Gênica de Plantas/fisiologia , Ácidos Indolacéticos/metabolismo , Oryza/metabolismo , RNA de Plantas/metabolismo , Transporte Biológico , Oryza/genética , Plantas Geneticamente Modificadas , RNA de Plantas/genética
11.
Mil Med Res ; 4: 2, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28116112

RESUMO

BACKGROUND: Hepatitis B is a disease that affects the liver and is caused by the hepatitis B virus (HBV). Hepatitis B is a serious public health problem in China. The objective of this study was to assess knowledge of and behaviours towards the transmission and prevention of hepatitis B of new military recruits in China. METHODS: A cross-sectional study was conducted among 800 new military recruits. A self-administered, structured questionnaire was used to collect information, and 727 questionnaires were returned completed. Analysis was performed using SPSS 18.0, and P < 0.05 was considered statistically significant. RESULTS: Of the respondents, 665 (91.5%) were male and 62 (8.5%) were female. The mean age was 18.9 ± 1.7 years. A total of 608 respondents (83.6%) demonstrated poor knowledge and 119 (16.4%) adequate knowledge about HBV. Older age, female and higher education level were statistically associated with a higher mean knowledge score. Multivariate logistic regression showed that age (OR = 3.040, 95%CI 1.724-5.359, P < 0.001) and gender (OR = 1.791, 95%CI 1.325-2.421, P < 0.001) were significantly associated with appropriate behavioural practices towards prevention of HBV. CONCLUSION: Against a backdrop of high HBV prevalence in China, new military recruits had poor knowledge of HBV. New recruits need better education about HBV to assist in reducing and preventing HBV infection.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hepatite B/complicações , Militares/psicologia , Adolescente , China , Estudos Transversais , Feminino , Hepatite B/diagnóstico , Vírus da Hepatite B/patogenicidade , Humanos , Masculino , Inquéritos e Questionários , Adulto Jovem
12.
Jpn J Clin Oncol ; 44(8): 711-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24855686

RESUMO

OBJECTIVE: Clinical trials suggest that combining transcatheter arterial chemoembolization with sorafenib in patients with advanced hepatocellular carcinoma shows a superior safety and tolerability profile. Our study aimed to retrospectively analyze the utility and prognostic factors of this combined therapy in these patients. METHODS: Patients with advanced hepatocellular carcinoma, treated by transcatheter arterial chemoembolization and sorafenib subsequently, between February 2010 and September 2012 in our hospital, were retrospectively analyzed. After sorafenib treatment for 12 weeks, abdominal enhanced computed tomography or magnetic resonance imaging was used to evaluate short-term outcomes and clinical benefit rate. Overall survival and adverse events were recorded during follow-up. Univariate and multivariate analyses were used to identify relationships between baseline characteristics and overall survival. RESULTS: Fifty-one advanced hepatocellular carcinoma patients were included. Common adverse events for sorafenib were hand-foot skin reaction, alopecia, diarrhea, anorexia and fatigue. The clinical benefit rate was 64% and the median survival time was 7.5 months. Median survival of patients with and without portal vein tumor thrombi was 6.0 months and 10.3 months (P < 0.001), respectively. Median survival of patients with cholinesterase ≥5000 U/l and < 5000 U/l was 10.6 months and 6.1 months (P < 0.001), respectively. Multivariate analysis identified the presence of portal vein tumor thrombi and low cholinesterase level as independent negative predictors of survival. CONCLUSIONS: Combining sorafenib and transcatheter arterial chemoembolization was safe and effective for advanced hepatocellular carcinoma patients with extrahepatic spread but without portal vein tumor thrombi. Portal vein tumor thrombi and cholinesterase level are independent predictors of prognosis following this combined therapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Alopecia/etiologia , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Esquema de Medicação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Sorafenibe , Tromboembolia Venosa/etiologia
13.
Zhonghua Gan Zang Bing Za Zhi ; 21(2): 125-8, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23663885

RESUMO

OBJECTIVE: To characterize the clinical, laboratory, imaging and pathological features of primary sclerosing cholangitis (PSC) and investigate the impact of ursodeoxycholic acid (UDCA) therapy on patient prognosis. METHODS: The medical records of 22 patients diagnosed with PSC between 2002 and 2011 were retrospectively reviewed. The PSC diagnosis had been made in patients with suspect biochemical abnormalities following evaluation by magnetic resonance cholangiopancreatography (MRCP) and/or endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). Fibrosis and inflammation were assessed by immunohistochemical analyses of tissue biopsies. Outcome of patients treated with UDCA (13-15 mg/kg/day, oral) were compared to that of patients without UDCA treatment by the X2 or corrected X2 tests. RESULTS: Among the 22 PSC patients, the majority was male (n=15) and presented with fatigue, dark urine, and body weight loss (n=15). Four cases had ulcerative colitis. At admission, all 22 cases showed elevated levels of alkaline phosphatase[ALP: (348+/-184) U/L], 19 cases showed elevated alanine aminotransferase [ALT: (94.0+/-67.0) U/L] and aspartate aminotransferase [AST: (98.0+/-67.0) U/L], and 15 cases showed elevated levels of total bilirubin (99.0+/-115.0) mumol/L and direct bilirubin (74.4+/-92.4 mumol/L. ERCP examination showed segmental intrahepatic bile duct stenosis with expansion, and stiff and enlarged gallbladder bile ducts, but unclear findings for the common bile ducts and pancreatic ducts. MRCP showed beading of the intrahepatic bile duct, stiffness of the bile duct wall, and dilation of the common bile duct. Fibrosis and inflammation were observed in the bile ducts, along with hyperplasia and the typical features of "onion skin" fibrosis and fibrous obliterative cholangitis. Five of the 10 patients treated with UDCA improved, and seven of the 12 patients in the non-UDCA treatment group improved. There was no statistically significant difference in outcome between the groups (paired X2=0.333, corrected X2=0.083, P more than 0.05). CONCLUSION: PSC patients were predominantly male and the common clinical manifestations were fatigue, dark urine, and body weight loss. At admission, serum biochemical indicators of cholangitis were increased significantly and subsequent imaging studies confirmed the suspected diagnosis by showing obvious characteristic changes. UDCA treatment did not significantly improve patient prognosis.


Assuntos
Colangite Esclerosante/diagnóstico por imagem , Colangite Esclerosante/patologia , Adulto , Colangiografia/métodos , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
14.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(2): 233-7, 2013 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-23591343

RESUMO

OBJECTIVE: To investigate the autoantibody profile and its clinical implication in the patients with primary biliary cirrhosis. METHODS: During the period of 2008 to 2010,123 patients with primary biliary cirrhosis (PBC) in our hospital were enrolled in this study, of whom, 70 patients were with cirrhosis and 53 without cirrhosis, The autoantibody profile was tested for each patient by using immunoblotting and indirect immunofluorescence. RESULTS: Of the 123 PBC patients with liver cirrhosis, 49% were positive with serum ANA positive; 47%, 51%, 54%, 31% and 49% were positive with serum anti-nuclear antibodies (ANA), anti-mitochondrial antibodies-M2 (AMA-M2), anti-promyelocytic leukemia (anti-PML), anti-sp100 antibodies (anti-sp100), anti-Ro-52 antibody (anti-52KD), respectively. By contrast, of the PBC patients without liver cirrhosis, only 38%, 37%, 51%, 60%, 30% and 51% were positive with serum ANA, AMA, AMA-M2, anti-PML, anti-sp100 and anti-52KD, respectively.There was the statistical difference between the two groups. In addition, it was also found that the anti-gp210 antibody positive group had a higher Mayo risk score,lower serum albumin and severe cholestasis and impaired liver function when compared with anti-gp210 antibody negative patients. CONCLUSION: Our data indicate that serum AMA is helpful for early diagnosis of PBC, and in particular, serum ANA positivity can help make a diagnosis for the AMA-negative patients. These indicate that anti-gp210 antibodies appear in the late course of PBC.Anti-gp210 positive PBC patients have more severe cholestasis and liver dysfunction.


Assuntos
Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Cirrose Hepática Biliar/imunologia , Mitocôndrias Hepáticas/imunologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complexo de Proteínas Formadoras de Poros Nucleares/imunologia , Estudos Retrospectivos
15.
Zhonghua Gan Zang Bing Za Zhi ; 20(7): 487-91, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-23044231

RESUMO

OBJECTIVE: To evaluate the safety of human umbilical cord derived-mesenchymal stem cell (UC-MSC) transplantation therapy in patients with decompensated liver cirrhosis. METHODS: UC-MSCs were transplanted intravenously into patients with decompensated liver cirrhosis. Serum levels of glucose (GLU), total cholesterol (TC), blood urea nitrogen (BUN), alpha fetoprotein (AFP), white blood cells (WBC), and prothrombin activity (PA) were detected at different time points after UC-MSCs transplantation. RESULTS: Most UC-MSC transplanted patients experienced an improvement in quality of life, to varying degrees. With the exception of low-grade fever in a few patients, side effects and oncogenic events were rare (treatment group: 1/38 vs. control group: 1/16; P more than 0.05). The UC-MSCs transplantation showed no effect on GLU, TC, BUN, AFP, WBC, or PA. CONCLUSION: UC-MSCs transplantation in patients with decompensated liver cirrhosis is safe and may improve the patient's quality of life.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Cirrose Hepática/cirurgia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 27(6): 668-70, 2011 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-21651872

RESUMO

AIM: This study attempted to investigate the features of Treg cells in peripheral blood and liver of patients with primary hepatocellular carcinoma (HCC). METHODS: Peripheral blood samples were obtained from 30 HCC patients and 30 healthy control subjects, then were quantitatively analyzed for Treg cells by using flow cytometry. Liver infiltrating lymphocytes (LIL) isolated from resected tumor samples of 7 HCC patients were simultaneously analyzed. RESULTS: There was a significant increase in the frequency of peripheral Treg cells in HCC patients compared with healthy controls (P < 0.01). Furthermore, we also found that there was a higher frequency of infiltrated Treg within tumor samples than the counterpart in non-tumor region (P < 0.05). In addition, CD4(+) CD25(low) and CD4(+) CD25(-) T cells isolated from resected tumor samples were found to express higher level of FOXP3 molecules. CONCLUSION: Our findings showed that a dramatic increasing increase of Treg in peripheral blood and liver tissue of HCC patients may be associated with the significant increased development of Treg, which favors the disease progression through the suppressive effect of Treg on host immune response in these patients.


Assuntos
Carcinoma Hepatocelular/patologia , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Hepáticas/patologia , Fígado/patologia , Linfócitos do Interstício Tumoral/patologia , Linfócitos T Reguladores/patologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/cirurgia , Progressão da Doença , Feminino , Fatores de Transcrição Forkhead/sangue , Hepatectomia , Humanos , Fígado/metabolismo , Fígado/cirurgia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/cirurgia , Contagem de Linfócitos , Masculino , Linfócitos T Reguladores/metabolismo , Regulação para Cima
17.
PLoS One ; 6(3): e17484, 2011 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21390263

RESUMO

BACKGROUND: Extensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB) infection. Macrophages and infiltrating monocytes also participate in the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages. METHODOLOGY/PRINCIPAL FINDINGS: The frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT) carriers and 78 immune activated (IA) patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16(+) subsets, which were closely associated with serum alanine aminotransferase (ALT) levels and the liver histological activity index (HAI) scores. In addition, the increased CD16(+) monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16(-) monocytes/macrophages. Furthermore, peripheral blood CD16(+) monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores. CONCLUSIONS: These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease.


Assuntos
Hepatite B Crônica/imunologia , Inflamação/imunologia , Cirrose Hepática/imunologia , Fígado/patologia , Monócitos/imunologia , Receptores de IgG/metabolismo , Índice de Gravidade de Doença , Adolescente , Adulto , Proliferação de Células , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Humanos , Inflamação/complicações , Fígado/imunologia , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Células Th17/citologia , Células Th17/imunologia , Adulto Jovem
18.
PLoS One ; 5(11): e13869, 2010 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-21079784

RESUMO

BACKGROUND: Treatment with nucleotide analogs is known to be effective in inhibiting HBV replication; however, patients with chronic hepatitis B (CHB) often show a wide range of clinical responses to these drugs. Therefore, the identification of an early immunologic marker associated with the clinical outcomes in such cases is critical for the improved clinical management. In our study, we aimed to investigate whether the viral load in CHB patients affected the ratio of the number of regulatory T cells (Tregs) to the number of interleukin-17-producing helper (Th17) cells. Further, we evaluated the clinical implications of the alterations in this ratio. METHODOLOGY/PRINCIPAL FINDINGS: Nine patients seropositive for hepatitis B e antigen received entecavir monotherapy for 12 months and the percentages of Tregs and Th17 cells as well as the HBV-specific IL-17 productions in these patients were longitudinally analyzed. The entecavir-induced suppression of HBV replication was accompanied by a rapid increase in the number of Th17 cells, together with a decrease in Treg cells, which lead to a significant reduction of Treg/Th17 ratios. In addition, peripheral blood mononuclear cells (PBMCs) exhibited a decreased IL-17 production upon stimulation with the HBV core antigen in vitro. CONCLUSIONS: The inhibition of viral replication results in an increase in Th17 cells and concomitant decrease in Treg cells. This imbalance of Treg cells to Th17 cells might have an important role in HBV persistence during entecavir treatment.


Assuntos
Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Adolescente , Adulto , Alanina Transaminase/sangue , Antivirais/uso terapêutico , DNA Viral/sangue , DNA Viral/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Seguimentos , Guanina/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Interleucina-17/sangue , Interleucina-17/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Células Th17/citologia , Células Th17/imunologia , Fatores de Tempo , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem
19.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 26(6): 536-8, 2010 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-20487644

RESUMO

AIM: To investigate phenotypical and functional characteristics of the CD39(+);FoxP3(+);regulatory T (Treg) cells in humans. METHODS: We collected peripheral blood from 10 healthy volunteers and separated PBMC by using density gradient centrifugation, and then detected the expression of CTLA-4, HLA-DR, CD45RO and Ki-67 on CD39(+);FoxP3(+); and CD39(-);FoxP3(+);Treg cells by using flow cytometric analysis. [(3);H]-thymidine incorporation assay and ELISA were used to monitor the suppressive capacity of CD39(+); FoxP3(+); Treg cells on proliferation and IFN-gamma secretion of Treg-depleted PBMC. RESULTS: The expression of CTLA-4, HLA-DR, CD45RO and Ki-67 was significantly higher in CD39(+);FoxP3(+); Treg cells than those in CD39(-);FoxP3(+); Treg cells. The suppressive capacity of CD39(+);FoxP3(+); Treg cells on proliferation and IFN-gamma secretion of Treg-depleted PBMC was significantly higher than those of FoxP3(+);CD39(-);Treg cells. CONCLUSION: CD39(+);Fxop3(+);Treg subset may play an essential role in immune regulation of Treg, and CD39 can be used as a surface marker to identify the functional Treg cells.


Assuntos
Antígenos CD/metabolismo , Apirase/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Adulto , Antígeno CTLA-4 , Proliferação de Células , Células Cultivadas , Feminino , Antígenos HLA-DR/metabolismo , Humanos , Interferon gama/metabolismo , Antígeno Ki-67/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Masculino , Linfócitos T Reguladores/citologia
20.
J Gastroenterol ; 45(9): 968-78, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20411280

RESUMO

BACKGROUND: We carried out this study to evaluate the association between regulatory T cells (Treg) and prognosis and progression after cryoablation in patients with hepatitis-B virus-related hepatocellular carcinoma. METHODS: Peripheral Treg frequency in 111 patients with hepatocellular carcinoma (HCC) was detected by flow cytometry. Treg frequency and function were re-examined during patient follow up. A possible association between Treg and α-fetoprotein (AFP) was also analyzed, and the distribution of resident CD4(+) and CD8(+) T cells and FoxP3(+) T cells in the liver tissue of patients with HCC was examined by immunohistochemistry. RESULTS: Treg frequency significantly increased with disease progression. Our longitudinal study showed that Treg frequency had significantly decreased in 17 patients with HCC regression following cryoablation, but the frequency had dramatically increased in 14 patients with HCC recurrence or progression. Furthermore, AFP levels varied in a way comparable with Treg frequency in patients with elevated AFP recorded before therapy. Significantly increased suppressive effects of Treg on proliferation and cytokine secretion of CD8(+) and CD4(+) T cells were observed during follow up in patients with tumor progression, but not in patients with tumor response. Moreover, the numbers of CD8(+), CD4(+), and FoxP3(+) cells infiltrating the tumors around the cryotherapeutic zones were significantly decreased after argon-helium cryoablation, and this was associated with a reduction in the FoxP3/CD8 ratio. Importantly,increased quantities of circulating CD4(+)CD25(+)FoxP3(+) Treg and tumor infiltrating FoxP3(+) cells before cryoablation were associated with high recurrence or risk of progression in HCC patients after cryoablation. CONCLUSIONS: Treg variation is associated with tumor regression or progression in HCC following cryoablation and may be used as a marker to estimate HCC progression.


Assuntos
Carcinoma Hepatocelular/cirurgia , Criocirurgia/métodos , Neoplasias Hepáticas/cirurgia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/virologia , Progressão da Doença , Feminino , Citometria de Fluxo , Seguimentos , Hepatite B/complicações , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Resultado do Tratamento
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