RESUMO
Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.
Assuntos
Antivirais , Hepatite B Crônica , Humanos , Hepatite B Crônica/tratamento farmacológico , China/epidemiologia , Antivirais/uso terapêutico , Interferon-alfa/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Polietilenoglicóis/uso terapêuticoRESUMO
Objective: To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF). Methods: 220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ(2) test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results: There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group (Pâ <â 0.05). Among the 220 ACLF cases, 158 (71.82%) were infected with the hepatitis B virus (HBV). The incidence rate of infection during hospitalization was 69.09% (152/220). The common sites of infection were intraabdominal (57.07%) and pulmonary infection (29.29%). Pearson correlation analysis showed that PNI and MELD-Na were negatively correlated (râ =â -0.150, Pâ <â 0.05). Multivariate logistic analysis results showed that low PNI score (OR=0.916, 95%CI: 0.865~0.970), ascites (OR=4.243, 95%CI: 2.237~8.047), and hepatorenal syndrome (OR=4.082, 95%CI : 1.106~15.067) were risk factors for ACLF co-infection (Pâ <â 0.05). The ROC results showed that the PNI curve area (0.648) was higher than the MELD-Na score curve area (0.610, Pâ <â 0.05). The effectiveness of predicting infection risk when PNI was combined with ascites and hepatorenal syndrome complications was raised. Patients with co-infections had a good predictive effect when PNI ≤ 40.625. The sensitivity and specificity were 84.2% and 41.2%, respectively. Conclusion: Low PNI score and ACLF co-infection have a close correlation. Therefore, PNI has a certain appraisal value for ACLF co-infection.
Assuntos
Insuficiência Hepática Crônica Agudizada , Coinfecção , Síndrome Hepatorrenal , Humanos , Insuficiência Hepática Crônica Agudizada/diagnóstico , Avaliação Nutricional , Prognóstico , Síndrome Hepatorrenal/complicações , Ascite/complicações , Estudos Retrospectivos , Vírus da Hepatite B , Curva ROCRESUMO
We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.
Assuntos
Lúpus Eritematoso Sistêmico , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Rituximab/uso terapêutico , Estudos Retrospectivos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Resultado do Tratamento , Imunoglobulina GRESUMO
The study aimed to analyze the efficacy and safety of rituximab in the treatment of 23 cases of lupus nephritis and explore the prospect of half-dose rituximab in lupus nephritis treatment. Twenty-three patients with lupus nephritis hospitalized in the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital from May 2013 to December 2021 were selected. Eighteen patients received rituximab 375 mg/m2 on the first and 14th days, 5 patients received 500 mg of rituximab on the first and 14th days, and rituximab was used as needed 6 months later. Methylprednisolone (80-120 mg) was given together with rituximab. Afterward, 1 mg/kg prednisone was used for 4 weeks, which was progressively tapered to maintenance doses or discontinued. B lymphocyte level, renal function, 24-h urine protein level, and systemic lupus erythematosus (SLE) disease activity index 2000 (SLEDAI2K) score before and after treatment were recorded. The efficacy and adverse reactions were analyzed. The results showed that 11 patients suffered from renal insufficiency [creatinine (162.7±58.6) µmol/L ] at baseline, while the creatinine level of 9 patients returned to normal 12 months after the treatment [ (66.3±10.1)µmol/L ]. Normal renal function of the other 12 patients was maintained during treatment. After 12 months, the 24-h urine protein level decreased from 4.00 (2.00,6.80) g in the baseline period to 0.10 (0.08,0.40) g. SLEDAI2K score decreased from 22 (18,26) in the baseline period to 3 (0,6) 12 months after the treatment. The B lymphocyte level reached 0.00 (0.00,0.01)% at 3 months. Of 23 patients, 13 patients achieved complete remission, and 7 patients achieved partial remission after 6 months of rituximab treatment. Five patients experienced adverse reactions related to rituximab, including 1 case of transfusion reaction, 1 case of perioral herpes with pulmonary infection, and 3 cases of decreased IgG levels. Therefore, rituximab regimen used in this study can be an effective treatment strategy for lupus nephritis.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Rituximab/efeitos adversos , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/induzido quimicamente , Creatinina , Metilprednisolona/uso terapêutico , Resultado do Tratamento , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Imunossupressores/uso terapêuticoRESUMO
Aim: To identify the key risk factors of intrauterine hepatitis B virus transmission (HBV) and its effect on the placenta and fetus. Methods: 425 infants born to hepatitis B surface antigen (HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study. The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg. Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission. Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress. Transmission electron microscopy was used to observe HBV Effects on placental tissue. Results: HBV intrauterine infection rate was 2.6% (11/425). Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants (P=0.011). Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>106 IU/ml than those with HBV DNA <106 IU/ml (12.2% vs. 1.8%; χ2=11.275, P=0.006), and (24.4% vs. 16.0%, χ2=3.993, P=0.046). Transmission electron microscopy showed that mitochondrial edema, endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>106 IU/ml than that of maternal HBV DNA<106 IU/ml (960 nm vs. 214 nm, Z=-2.782, P=0.005) in the placental tissue. Conclusion: Maternal HBV DNA>106 IU/ml is associated not only with intrauterine infection, but also with increased incidence of intrauterine distress and placental sub-microstructural changes, providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.
Assuntos
Hepatite B , Complicações Infecciosas na Gravidez , DNA Viral , Feminino , Sofrimento Fetal/tratamento farmacológico , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/genética , Humanos , Imunoglobulinas/uso terapêutico , Lactente , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Placenta , GravidezRESUMO
OBJECTIVE: Given that FK506 binding protein 51 (FKBP51) is upregulated in multiple cancers, we designed the present study to characterize its role as well as underlying regulatory mechanisms in glioma in the presence and absence of the chemotherapeutic carmustine (BCNU). MATERIALS AND METHODS: Through lentiviral overexpression and shRNA knockdown of FKBP51, we examined the effects on BT325 glioma cell proliferation, migration and invasion using quantitative reverse transcription PCR (qRT-PCR), CCK-8 assay, flow cytometry, and transwell assay. RESULTS: The upregulation of FKBP51 resulted in significantly decreased BT325 cell proliferation and cell viability, cell cycle arrest, reduced BCNU chemosensitivity and AKT pathway inactivation. However, FKBP51-overexpressed BT325 cells showed enhanced migration and invasion, which was supported by corresponding increase in phosphorylated IKKα (p-IKKα), MMP-2, and MMP-9 levels, as well as increased NF-κB p65 nuclear translocation. By contrast, FKBP51-suppressed BT325 cells showed excessive proliferation and BCNU resistance due to increased p-AKT activation and attenuated migration and invasion. CONCLUSIONS: We demonstrated that the effects of FKBP51 on BT325 glioma cell proliferation, migration, invasion and BCNU chemosensitization are modulated via the AKT and NF-κB pathways. Furthermore, our findings suggest the potential of FKBP51 as a prognostic glioma biomarker and an indicator of patient response to chemotherapy.
Assuntos
Biomarcadores Tumorais/metabolismo , Glioma/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo , Antineoplásicos Alquilantes/farmacologia , Biomarcadores Tumorais/genética , Carmustina/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Proteínas de Ligação a Tacrolimo/genética , Células Tumorais CultivadasRESUMO
Objective: To explore the role of extracellular histones in the pathogenesis of coal worker's pneumoconiosis (CWP) , the relationship of extracellular histones in plasma with pulmonary fibrosis caused by coal mine dust was analyzed, and the stimulating effect of extracellular histones on fibroblast proliferation was studied. Methods: In May 2019, a total of 220 coal mine dust exposure workers (including coal miners and CWP patients) who visited the occupational disease outpatient department of Peking University Third Hospital from 2012 to 2015 were enrolled in the study. According to the classification of small opacity profusion (SOP) in chest radiograph for pneumoconiosis diagnosis (category 0, 1, 2, 3) , 61 coal miners were in category 0 SOP, 65 coal miners were in category 1 SOP, 56 coal miners were in category 2 SOP and 38 coal miners were in category 3 SOP. The plasma levels of extracellular histone H4 and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunosorbent assay (ELISA) kit. The stimulating effects of CWP patients' plasma and calf thymus histones (CTHs) on fibroblast and the antagonizing effect of anti-H4 antibody were investigated by fibroblast proliferation experiment in vitro. Results: Among the study subjects, there were 195 males (88.6%, 195/220) and 25 females (11.4%, 25/220) , age (55.1±7.2) years, coal mine dust exposure time (16.3±4.4) years. The plasma concentrations of histone H4 in the coal miners with category 0, 1, 2 and 3 SOP were (3.92±1.75) ã(9.84±4.17) ã(14.35±5.52) and (17.83±7.69) µg/ml, respectively. There were significant differences among the four groups (P<0.01) . The plasma level of histone H4 was positively correlated with the plasma level of PDGF in the coal miners (r=0.769, P<0.01) . Compared with healthy control plasma group, the cell proliferation percentages of patients' plasma group (272%±87%) and CTH group (283%±84%) were significantly increased (P<0.05) . Compared with patients' plasma group, the cell proliferation percentage of patients' plasma+anti-H4 antibody group (185%±66%) was significantly decreased (P<0.05) . Compared with CTH group, the cell proliferation percentage of CTH+anti-H4 antibody group (167%±59%) was significantly decreased (P<0.05) . Conclusion: Extracellular histones in plasma are associated with pulmonary fibrosis in patients with CWP. Studies in vitro have shown that extracellular histones can promote proliferation of pulmonary fibroblasts. It is suggested that extracellular histones can be important biomarkers for pulmonary fibrosis caused by coal mine dust.
Assuntos
Minas de Carvão , Mineradores , Doenças Profissionais , Pneumoconiose , Antracose , Carvão Mineral , Feminino , Histonas , Humanos , MasculinoAssuntos
Vírus da Hepatite B , Hepatite B/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Guias de Prática Clínica como Assunto , Complicações Infecciosas na Gravidez/prevenção & controle , Criança , China , Feminino , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B , Humanos , Gravidez , Complicações Infecciosas na Gravidez/virologiaRESUMO
Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion: Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Antivirais/efeitos adversos , China , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the effect of sulfur dioxide (SO2) on the apoptosis of alveolar macrophage (AM) in lung protection of limb ischemia/reperfusion (I/R) induced acute lung injury (ALI), and to find a new target for the control of inflammatory response. METHODS: Twenty pathogen-free, adult male Sprague-Dawley (SD) rats (180-230 g) were used in this study. Five rats were to be used for limb ischemia/reperfusion, then plasma was extracted as ischemia/reperfusion serum stimulation. Fifteen rats were to be used for extracting AM by bronchoalveolar lavage. The AM was isolated and cultured, then the cell count was adjusted to 1×106/mL, and randomly divided into the following 4 groups (n=6): control group, I/R group, SO2 group, and I/R+SO2 group. The I/R group was given ischemia/reperfusion serum (500 µg/L) to stimulate 6 h; the SO2 group was given an SO2 donor, Na2SO3/NaHSO3 [(0.54 mmol/kg) / (0.18 mmol/kg)]; and the I/R+SO2 group was given the same ischemia/reperfusion serum and Na2SO3/NaHSO3 at the same time. The level of mitochondrial membrane potential, the state of mitochondrial permeability transition pore (mPTP), the rate of AM apoptosis, the expression of Bcl-2 and Caspase-3 proteins were detected by flow cytometry, microplate reader and Western blotting. RESULTS: Compared with the control group, in the I/R group, the ratio of red to green fluorescence and the absorbance decreased significantly, the percentage of apoptotic cells increased obviously, the apoptotic rate was 43.81%±2.40%, Caspase-3 protein expression increased, Bcl-2 protein expression decreased. While compared with the I/R group, in the I/R+SO2 group, the ratio of red to green fluorescence and the absorbance increased significantly; the apoptotic rate decreased to 37.01%±1.93%, Caspase-3 protein expression decreased, Bcl-2 protein expression increased. CONCLUSION: Exogenous SO2 has the effect of accelerating AM apoptosis by stimulating mPTP to open and mitochondrial membrane potential to decrease; besides, exogenous SO2 could stimulate AM to secrete more anti-inflammatory cytokines and less inflammatory cytokines. In conclusion, exogenous SO2 can reduce macrophage apoptosis by inhibiting mitochondrial pathways.
Assuntos
Lesão Pulmonar Aguda , Traumatismo por Reperfusão , Animais , Apoptose , Isquemia , Macrófagos Alveolares , Masculino , Ratos , Ratos Sprague-Dawley , Dióxido de EnxofreRESUMO
To investigate the effects of dietary phytosterols (PS) on growth performance, antioxidant status, and meat quality of Partridge Shank chickens, a total of 256 1-day-old male Partridge Shank chicks were randomly assigned into 4 dietary treatments, and each of them replicated 8 times with 8 chicks per replicate. Birds in the 4 treatments were fed a basal diet supplemented with 0 (Control group), 20, 40, and 80 mg/kg PS for 50 D, respectively. Dietary supplementation of PS quadratically increased average daily gain of chickens during the grower and overall periods, whereas linearly decreased the feed-to-gain ratio during the starter period. Compared with control group, a significant increase in average daily gain during the grower and overall periods was observed in chickens fed the basal diet supplemented with 40 mg/kg PS. Increasing PS addition linearly increased serum glutathione peroxidase (GSH-Px) activity at 21 and 50 D and hepatic GSH-Px and superoxide dismutase activities at 21 D, whereas linearly decreased malondialdehyde concentration of breast muscle at 50 D. Meanwhile, 40 mg/kg PS supplementation significantly increased serum GSH-Px activity, and hepatic superoxide dismutase and GSH-Px activities at 21 D as compared with the control. PS supplementation linearly and quadratically decreased drip loss (24 and 48 h postmortem) and luminance value (24 h postmortem) of breast muscle in broilers at 50 D, and there was statistical difference between the control and PS-supplemented group. In conclusion, PS supplementation can improve growth performance, antioxidant status, and meat quality of Partridge Shank chickens, with its optimum level in Partridge Shank chickens' diet being 40 mg/kg.
Assuntos
Antioxidantes/metabolismo , Galinhas/fisiologia , Carne/análise , Fitosteróis/metabolismo , Ração Animal/análise , Animais , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Masculino , Fitosteróis/administração & dosagem , Distribuição AleatóriaRESUMO
BACKGROUND: Hepatitis C virus (HCV) infection in patients undergoing haemodialysis is prevalent and aggressive. The treatment of chronic hepatitis C has been revolutionised by the advent of direct-acting antivirals (DAAs). However, the safety, efficacy, and tolerance of DAAs in the treatment of acute HCV infection in patients with end-stage renal disease who are on haemodialysis are unknown. AIM: To evaluate the safety and efficacy of sofosbuvir plus daclatasvir in this specific, difficult-to-treat population. METHODS: We conducted a prospective and observational study of end-stage renal disease patients who were undergoing haemodialysis and were acutely infected with HCV. Patients received a half dose of sofosbuvir (200 mg) and a full dose of daclatasvir (60 mg) daily. The primary endpoint was the proportion of patients with sustained virological responses (SVRs); the other primary outcomes were safety and tolerability. RESULTS: Thirty-three patients were enrolled in the study. The median HCV RNA viral load at baseline was 6.8 log10 IU/mL. Twenty-four patients were infected with HCV genotype 2a, seven patients with 1b, and two patients with 2a+1b. All patients achieved a SVR at 12 weeks after the end of treatment. The treatment was well tolerated, and there were no drug-related serious adverse events. CONCLUSION: A half dose of sofosbuvir (200 mg once daily) plus a full dose of daclatasvir (60 mg once daily) were suitable for the treatment of acute HCV-infected patients who were undergoing end-stage renal disease and were on haemodialysis.
Assuntos
Antivirais , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal , Sofosbuvir , Doença Aguda , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carbamatos , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirrolidinas , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Resultado do Tratamento , Valina/análogos & derivados , Adulto JovemRESUMO
Objective: To investigate the association between single nucleotide polymorphisms (SNPs) of rs3130542 and rs4821116 in the HLA-C and UBE2L3 genes and the effect of telbivudine antiviral therapy during pregnancy in HBeAg-positive mothers through a large-sample control study, and to provide a basis for the development of individualized blocking strategies for pregnant women with a high viral load. Methods: The genotypes of rs3130542 and rs4821116 were determined for 312 pregnant women with a high viral load who received telbivudine antiviral therapy during the second or third trimester of pregnancy, and the dominant model, recessive model, and additive model were used to analyze the association between the genotypes of these two loci and the reduction in HBV DNA load. The Shapiro-Wilk test and the Levene test were used to evaluate data normality and homogeneity of variances, and the t-test or the non-parametric Mann-Whitney U test was selected based on data type and was used for the comparison of means between groups. The Hardy-Weinberg equilibrium was used to determine the genotype of SNPs, and the dominant model, recessive model, and additive model were used for analysis. Results: Mothers with an AA/AG genotype of rs3130542 in the HLA-C gene had a significantly higher probability of HBV DNA load ≥10(3) IU/ml at the time of delivery (P < 0.05) and a significantly higher risk of failure in the prevention of mother-to-child transmission, no matter whether they started to take telbivudine at week 24 or 28 of pregnancy. The association between the genotype of rs4821116 in the UBE2L3 gene and the reduction in viral load in pregnant women needed to be confirmed by studies with a larger sample size. Conclusion: Pregnant women with a high viral load and an AA/AG genotype of rs3130542 in the HLA-C gene tend to have poor response to antiviral therapy during pregnancy, and early antiviral intervention is recommended for such patients.
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Antivirais/uso terapêutico , Antígenos HLA-C/genética , Hepatite B Crônica/tratamento farmacológico , Telbivudina/uso terapêutico , Enzimas de Conjugação de Ubiquitina/genética , Criança , DNA Viral , Feminino , Humanos , Polimorfismo de Nucleotídeo Único , Gravidez , Carga ViralRESUMO
The article "Targeting of miR-20a against CFLAR to potentiate TRAIL-induced apoptotic sensitivity in HepG2 cells" by Y. Wang, Y.-R. Zhao, A.-Y. Zhang, J. Ma, Z.-Z. Wang, X. Zhang, published in Eur Rev Med Pharmacol Sci 2017; 21 (9): 2087-2097 has been withdrawn.
Assuntos
Apoptose/efeitos dos fármacos , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/biossíntese , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Adulto , Idoso , Animais , Carcinoma Hepatocelular/metabolismo , Caspase 3/metabolismo , Caspase 8/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , RatosRESUMO
Objective: To investigate the impact factors for central neck lymph node metastases(CLNM) of papillary thyroid carcinoma(PTC). Methods: A total of 498 patients with PTC who underwent total or hemi-thyroidectomy plus central neck lymph node dissection between January 2014 and July 2016 were included. Univariate and multivariate analyses were performed to identify clinicopathological characteristics, thyroid function parameters and US findings that associated with CLNM of PTC. A nomogram was developed to predict the probability of CLNM. The receiver operating characteristic curve(ROC) was used to estimate the efficiency of the nomogram. Results: Among 498 patients, 284 patients were affected by CNLM. The sensitivity and specificity of US in predicting PTC metastasis in the central neck were 31.3% and 88.3%, respectively. Univariate and multivariate analyses showed that gender, age, number and size of suspicious malignant nodules in thyroid, and suspicious lymph node metastasis detected by ultrasonography were independently correlated with CLNM. The ROC showed that the AUC was 0.748, with sensitivity of 80.8%, and specificity of 59.8%. Conclusions: Gender, age, number and size of suspicious malignant nodules in thyroid, suspicious lymph node metastasis were predictive factors for CLNM in patients with PTC. The nomogram developed based on related factors with CLNM is more sensitive than sonographic central neck lymph node features in predicting the probability of CLNM.
Assuntos
Carcinoma Papilar/secundário , Linfonodos/patologia , Metástase Linfática , Esvaziamento Cervical , Nomogramas , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Fatores Etários , Análise de Variância , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Feminino , Humanos , Masculino , Pescoço , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Fatores Sexuais , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , UltrassonografiaRESUMO
OBJECTIVE: Elevated expression of caspase-8 (CASP8) and Fas-associating protein with a novel death domain (FADD)-like apoptosis regulator (CFLAR) increases sensitivity against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell apoptosis, but with an unclear mechanism. A previous study showed decreased microRNA-20a (miR-20a) expression in hepatocellular carcinoma (HCC) patient's tumor tissues. Bioinformatics analysis showed potential targeting relationship between the 3-UTR of CFLAR and miR-20a. This study investigated if miR-20a played a role in regulating CFLAR expression and HCC apoptosis. PATIENTS AND METHODS: Expressions of miR-20a and CFLAR in model rat HCC tissues were compared to normal tissues. HCC patients were also collected for measuring miR-20a and CFLAR expressions between tumor and adjacent tissues. Dual-luciferase reporter gene assay was performed to evaluate the relationship between miR-20a and CFLAR. Cultured HepG2 cells treated with 120 ng/ml TRAIL were mixed with miR-20a mimic and/or si-CFLAR followed by measurement of Caspase-8/3 activity and cell apoptosis by flow cytometry, cell proliferation by MTT assay and protein expression by Western blot. RESULTS: MiR-20a expression was significantly decreased in rat HCC tissues, while CFLAR was over-expressed. HCC patients had lower miR-20a level and higher CFLAR level in tumor tissues. MiR-20a targeted 3'-UTR of CFLAR to inhibit its expression. TRAIL remarkably up-regulated CFLAR expression, whilst inhibiting miR-20a expression and/or silencing CFLAR significantly potentiated caspase-8 and caspase-3 activity, enhanced sensitivity of HepG2 cells towards TRAIL-induced cell apoptosis, and decreased cell proliferative function. CONCLUSIONS: HCC had lower miR-20 and higher CFLAR expression. MiR-20a targeted and inhibited CFLAR expression, facilitated activation of caspase-8 and caspase-3, and enhanced sensitivity of HepG2 cells towards TRAIL-induced apoptosis, and subsequently reduced cell proliferation.
Assuntos
Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Adulto , Idoso , Animais , Apoptose , Caspase 3/metabolismo , Feminino , Células Hep G2 , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley , Ligante Indutor de Apoptose Relacionado a TNF/metabolismoRESUMO
OBJECTIVE: This study investigated the effects of immune complexes (ICs) on tumor necrosis factor α (TNF-α) and B cell-activating factor (BAFF) production from U937 cells and further explored the mechanism. MATERIALS AND METHODS: U937 cells were incubated with necrosis supernatant or systemic lupus erythematosus (SLE) sera alone, or their combination. The expression of TNF-α and BAFF was determined by Real-time polymerase chain reaction and enzyme-linked immunosorbent assay. High mobility group box protein 1(HMGB1) A-box was produced by gene recombination. HMGB1 A-box and anti-receptor for advanced glycation end products (RAGE) antibody were adopted in the blocking experiments. The importance of DNA for cytokine induction was investigated by DNase treatment. RESULTS: The combination of necrosis supernatant and SLE sera induced the expression of TNF-α and BAFF significantly increased compared to necrosis supernatant or SLE sera alone. Recombinant HMGB1 A-box protein was purified, and TNF-α and BAFF production, which were induced by this combination, was blocked via HMGB1 A-box and anti-RAGE antibody. Moreover, we found that DNA component is important for the immunostimulatory activity of this combination. CONCLUSIONS: ICs containing DNA can promote TNF-α and BAFF production in U937 cells, and this process can be mediated by HMGB1 and RAGE. One possible mechanism of increasing BAFF production in SLE is proposed in this study whereby B cell activation, antibody production and ICs stimulated monocytes may create a vicious cycle that leads to B cell hyperactivity, which can be of importance for SLE etiopathogenesis.
Assuntos
Complexo Antígeno-Anticorpo , Antígenos de Neoplasias/metabolismo , Fator Ativador de Células B/metabolismo , Proteína HMGB1/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Lúpus Eritematoso Sistêmico/sangue , Células U937RESUMO
The new allele A*02:355 differs from A* 02:03:01 at positions 98 (TâA) and 102(AâC) resulting in an amino acid exchange F9âT. Interallelic sequence exchange is more likely the mechanism of its origination. The amino acid replacement influences the HLA peptide binding cleft and might have significant functional effects.
Assuntos
Alelos , Substituição de Aminoácidos , Antígeno HLA-A2/genética , Mutação , Povo Asiático , Sequência de Bases , Éxons , Expressão Gênica , Antígeno HLA-A2/imunologia , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA , Doadores de TecidosRESUMO
OBJECTIVE: To investigate the characteristics of hepatitis B virus (HBV) transmission among family members in families with familial clustering of HBV infection and poor outcomes, as well as the prevalence and distribution characteristics of HBsAg in offspring with different parental HBsAg status. METHODS: The general information of each member in families with poor outcomes were collected from 2007 to 2010, and serological test was performed to analyze the prevalence and distribution of HBsAg in family members. The chi-square test or Fisher's exact test was used to analyze and compare the sex of offspring and the prevalence of HBsAg in them in 266 nuclear families with different paternal and maternal HBsAg status. RESULTS: The positive rates of HBsAg in parents, siblings, children, and spouses of the probands were 20%, 88.2%, 76.8%, and 9.5%, respectively. The nuclear families with HBsAg-positive fathers and HBsAg-negative mothers had a significantly increased proportion of male offspring (male/female ratio = 2.02) compared with those with HBsAg-positive mothers and HBsAg-negative fathers (1.22) or those with HBsAg-negative fathers and mothers (0.96). In addition, in the nuclear families with HBsAg-positive fathers and HBsAg-negative mothers, the male offspring had a significantly higher HBsAg positive rate than female offspring (37.4% vs 13.8%), while in those with HBsAg-positive mothers and HBsAg-negative fathers or those with HBsAg-negative fathers and mothers, HBsAg positive rate showed no significant difference between male and female offspring. CONCLUSION: In families with familial clustering of HBV infection and poor outcomes, mother-to-child transmission is still the major route of HBV transmission, but father-to-child transmission also plays a role in HBV transmission in this special population. Positive HBsAg in fathers is associated with the increased proportion of male offspring, and father-to-son transmission of HBV is higher than father-to-daughter transmission.