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Objective@#To investigate the correlation between the frequency and function of early plasmacytoid dendritic cells (pDC) and the treatment response in patients with HBeAg-positive chronic hepatitis B receiving entecavir (ETV).@*Methods@#Patients with HBeAg-positive chronic hepatitis B were enrolled. Antiviral therapy with ETV, serum serological markerso hepatitis B virs (HBV) infection and liver function (HBV DNA load, HBsAg/anti-HBs, HBeAg and anti-HBe levels, and ALT levels) were monitored every three months before and during treatment; the efficacy of ETV was assessed by changes in the level of HBV DNA. Peripheral venous blood was collected before treatment, at 12 weeks and 24 weeks, respectively. Flow cytometry was used to detect the frequency of peripheral blood pDC and the surface co-stimulatory molecule CD86. The baseline and early treatment (12 weeks and 24 weeks) pDC frequency and functional changes were analyzed.@*Results@#Of the 100 patients with chronic hepatitis B, 45 patients received ETV treatment and 48 weeks of follow-up. Within 48 weeks of ETV treatment, HBsAg levels decreased by 0.53±0.78 log IU/mL; HBeAg decreased by 816.61S/CO, and HBeAg seroconversion occurred in 4 cases; HBV DNA content decreased by 6.04±1.12 log IU/mL, in 33 cases (73%) the HBV DNA became undetectable, in 43 cases ALT kept normal continuously for more than 3 months. In the early stage of ETV treatment, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes. In ETV-treated HBV DNA responders, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes; HBV DNA non-responders had a significant increase in pDC%, but CD86+ pDC% decreased significantly, and CD86MFI and CD86ABC showed no significant changes. The decrease in HBsAg and HBeAg levels in ETV treated patients was not significantly associated with early pDC%, CD86+ pDC%, CD86MFI and CD86ABC changes.@*Conclusions@#ETV treatment can directly inhibit the replication of HBV DNA, but does not enhance the function of immune cells.
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Objective@#We aimed to evaluate changes towards liver fibrosis during entecavir(ETV)treatment by non-invasive fibrosis markers in chronic hepatitis B (CHB) patients who need antiviral therapy.@*Methods@#Totally 303 HBeAg negative treatment-naive CHB patients were enrolled and liver biopsy was performed before starting antiviral therapy in this study. Totally 196 patients who need antiviral therapy were treated with ETV for at least 3 years. A clinical and virological evaluation was performed at baseline and again after 1, 2 and 3 years during ETV treatment. AST-to-platelet ratio index (APRI) was used to assess dynamic changes of liver fibrosis in HBeAg negative CHB patients after 1, 2, 3 years of ETV treatment.@*Results@#All enrolled patients experienced liver biopsy at baseline. According to Metavir fibrosis stages, F1, F2, F3 and F4 patients were 107, 125, 54 and 17, respectively. The APRI score enabled the correct identification of patients with severe fibrosis (METAVIR F3-F4). The APRI values significantly decreased in F2 and F3 patients after 1 year ETV therapy (P<0.01). But for F4 patients, APRI values decreased significantly at year 3 (P<0.05).@*Conclusions@#APRI values decreased significantly during ETV treatment in HBeAg-negative CHB patients indicating that these noninvasive fibrosis tests might be useful for monitoring improvement of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.
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Objective@#To explore the association between the efficacy of peg-IFN and the complexity of TP and RT regions of hepatitis B virus (HBV) in chronic hepatitis B.@*Methods@#Patients with HBeAg positive, HBV DNA positive chronic hepatitis B were given peg-interferon 180 μg once a week for subcutaneous injection, and baseline information was collected from baseline and after 12 weeks’ treatment. The baseline HBV DNA TP and RT fragments were amplified, database, high-throughput sequencing, and the average genetic distance calculation.@*Results@#Data of 108 patients were analyzed by logistic regression. RT area fragment Markov distance and TP area fragment Shannon quotient for HBV DNA response were calculated. ALT level is good for HBeAg response. HBsAg level is bad for HBsAg response.@*Conclusions@#The complexity of the baseline TP and RT regions may be associated with the efficacy of peg-interferon therapy for CHB.
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Thyroid nodules are common diseases in neck. As the most commonly used imaging technique for the evaluation of thyroid nodules, ultrasound has a high accuracy of differentiating malignant from benign thyroid nodules. However, there are inter-observer variabilities in the diagnosis and description of thyroid nodules by ultrasound. And terms used to describe nodules are often poorly defined, which is the major cause of inter-observer variabilities. Several authors have recently described a standardized risk stratification system called the Thyroid Imaging, Reporting and Data System (TI-RADS), modeled on the BI-RADS system for breast imaging. And then they recommended corresponding fine-needle aspiration (FNA) or follow-up according to risk stratification. Despite these efforts, none of these TIRADS classifications have been widely adopted. With the widely use of high-quality imaging, incidental thyroid nodules (ITNs), which are defined as nodules not previously detected or suspected clinically, are increasingly prevalent. Most ITNs are small and benign. And incidental thyroid malignancies typically have indolent behavior. There is no unified standard for clinical management of ITNs by now. As a result, American College of Radiology (ACR) formed the Incidental Thyroid Findings Committee and ACR TI-RADS Committee. They published "Managing ITNs Detected on Imaging: White Paper of the ACR Incidental Thyroid Findings Committee", "Thyroid Ultrasound Reporting Lexicon: White Paper of the ACR TIRADS Committee" and "ACR TI-RADS: White Paper of the ACR TI-RADS Committee" from 2015 to 2017. Through establishing these white papers, ACR tried to provide guidance regarding management of thyroid nodules on the basis of their ultrasound appearance, standardize the diagnostic approach to thyroid nodules through the development of a lexicon and recommend a practical approach to managing ITNs on CT, MRI, nuclear medicine and ultrasound studies.
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Objective@#To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied.@*Methods@#Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded.@*Results@#The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild.@*Conclusions@#The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.
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Objective@#To investigate the differences in frequency and function of natural killer cells (NK) between chronic hepatitis B (CHB) and acute hepatitis B (AHB).@*Methods@#Patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of NK, CD56dimNK, CD56brightNK and the expression of functional molecules IFNAR2 and NKp46 on the surface of NK cells were detected respectively among patients with CHB in IA phase, patients with AHB, and those recovered from AHB. At the same time, their correlations with ALT, HBV DNA and HBV markers were analyzed.@*Results@#Between IA and AHB, the frequencies of NK cells and NKp46dim NK cells in AHB cases were significantly lower than those in IA cases, but the frequency of NKp46high NK cells in AHB was higher than that in IA. For patients who recovered from AHB, the frequency of NK cells and NKp46dim NK cells increased; the varied ranges of frequencies of CD56dimNK, IFNAR2+ NK and NKp46+ NK cells were on the rise, while the frequency of NKp46high NK cells decreased after the recovery from AHB, and the varied ranges of CD56brightNK and IFNAR2MFI, NKp46MFI decreased. In AHB, HBVDNA loads were positively correlated with ALT levels. Before and after the recovery of AHB: ΔHBV DNA and ΔALT, Δ NK/LY (%) were positively correlated; ΔALT and ΔNKp46highNK/NK(%), ΔNKp46MFI, ΔIFNAR2MFI were positively correlated.@*Conclusions@#In CHB immune active phase, the activity of peripheral blood NK cells was too weak to remove the virus, but NK cells play an important role in eliminating the viruses and mediating liver tissue inflammation in AHB.
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The management of thyroid nodules can be classified into narrow-and broad-sense levels. The broad-sense procedures are used for special population and include screening,risk assessment of thyroid nodules,follow-up of benign thyroid nodules,surgical operation,post-operative follow-up,and assessment and treatment of recurrence and/or metastasis of thyroid cancer. The narrow-sense procedures are for individual patients and the whole process includes the assessment,supervision,treatment,and reassessment of thyroid lesion. Ultrasound plays different roles at different management stages. With the development of ultrasonic technology and improvement of diagnostic accuracy,ultrasound has gradually becoming an irreplaceable imaging tool in the diagnosis of thyroid nodules. In this article we review the history of thyroid ultrasound and the latest international guidelines on the management of thyroid nodules and differentiated thyroid cancer by focusing on the role of ultrasound throughout the management of thyroid nodules.
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Objective@#To investigate the differences in function of plasmacytoid dendritic cells (pDC) and CD4+ T helper cells (CD4+ Th cells) between acute hepatitis B (AHB) and chronic hepatitis B (CHB).@*Methods@#In this study, patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of pDC, CD86+ pDC, CD4+ T cells and their subsets, surface functional molecules were detected respectively among patients with chronic HBV infection in IA phase, patients with AHB, those recovered from AHB. Meanwhile, their correlations with ALT, HBV DNA and HBV markers were analyzed.@*Results@#The ALT level in AHB was significantly higher than that in IA, and inflammation was more obvious in AHB. Between IA and AHB, CD86+ pDC frequency and the mean fluorescence intensity of functional molecule CD86 (CD86MFI) were higher in IA than those in AHB, but the frequency of CD4+ T cells in AHB was higher than that in IA. For patients who got over AHB, the frequency of CD86+ pDC increased; Th1 were on the rise, while the frequencies of CD4+ T and Th2 decreased after the recovery of AHB, and Th2 / Th1 ratio decreased..In AHB, HBVDNA loads were positively correlated with ALT levels and Th2 frequencies.@*Conclusions@#In CHB immune active phase, CD86+ pDC with stimulating function played an important role, but the cellular immune response of CD4+ T cells decreased. In AHB inflammatory stage, CD4+ T cells played a strong cellular immune response, which result ed in viral clearance. Th2 cells regulation of CD4+ T cells played a dominant role, which was involved in the inflammatory response, and the cytotoxic role of Th1 cells during the recovery period was dominant, playing a strong cellular immune response, then the virus were completely eliminated.
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Objective@#To investigate the change of hepatitis B surface antibody (HBsAb) titer and its long-term protection and infection rates between 1 and 3-year-old children whose mothers were chronic hepatitis B pregnant woman with HBeAg positive and high viral load after successful blocking of mother-to-child transmission.@*Methods@#One-year-old children whose mothers were hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive, with HBV DNA≥106IU/ml were enrolled, then were followed up till 3 years old, and tested the five serological markers of hepatitis B and biochemical parameters at the age of one and three years respectively, and analyzed HBsAb titer, positive rate, negative rate and infection rate of 1 to 3-year-old children without enhanced vaccination; meanwhile, data of HBsAb titers at the age of 7 months were collected HBsAb titer, positive rate, and negative rate were analyzed.@*Results@#Totally 264 1-year-old children were enrolled into the study, including 178 children without enhanced vaccination between seven months and 1 year of age, and 114 children without enhanced vaccination between 1 year and 3 years of age. Our result showed that there were no infected children at the age between 1 and 3 years. HBsAb titer decreased from 7 months to 1 year old and dropped from 1 000 IU/L to 509.43 IU/L (P<0.05), and the antibody was still protective. From 1 year to 3 years old, HBsAb titer dropped from 466.72 IU/L to 67.3 IU/L (P< 0.05); at the age of 3 years, 60.52 % children were either weakly positive or negative, but still protective, but significantly less than those who had the reinforced vaccination. As a result , the children without the enhanced vaccination between 1 and 3 years of age were still at high risk.@*Conclusions@#If the antibody was protective at 7 months, children were not easily infected between 1 year and 3 years of age. At the age of 3, the antibody dropped to low or no responsive levels, and the children were still at high risk. It is necessary to take protective measures and supplement the vaccine.
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Objective To compare diagnostic values of the 2015 American Thyroid Association (ATA) Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer with the thyroid imaging reporting and data system (TI-RADS) for sonographic malignancy risk stratification of thyroid nodules.Methods From November 2011 to December 2015,485 thyroid nodules in 331 patients (mean age,42.9 years± 10.4)were included in this study.Characteristics includingsize,composition,shape(nonparallel or parallel),margin,echogenicity,calcifications and extrathyroidal extension of thyroid nodules were evaluated.Every nodule was stratificated by criteria set by TI-RADS and ATA guidelines,and malignant rate of each risk stratification were calculated and analysed.With pathology as the gold standard,different cutoff were taken to diagnose malignant nodules,and the sensitivity,specifity,positive predictive value,negativepredictive value and accuracy of the two methodologies were calculated at each cutoff.And the two methodologies were evaluated and measured by ROC curve.Finally their Kappa value were calculated at the best cutoff.Results Of the 485 thyroid nodules,96 were benign and 389 were malignant.The malignancy rates under TI-RADS category 2,3,4a,4b,4c,and 5 nodules were 0,12.0％ (3/25),22.2％ (10/45),29.8％ (14/47),99.2％ (261/363) and 100％ (101/101).Malignancy rates under ATA guidelines of benign,very low,low,intermediate,and high suspicion for malignancy were 0,12.5％ (1/8),16.1％ (10/62),27.7％ (13/47),and 99.2％ (365/368).There were significant differences inside each patterns (P ＜ 0.01) respectively and high correlation between risk stratification with TI-RADS (r=0.70) and ATA guidelines (r=0.83).Areas under the ROC curve of the TI-RADS and ATA guidelines classifications were 0.966 and 0.959.Best cut-off point for diagnosing malignant by TI-RADS and ATA guideline classifications were ≥ 4c and ≥ high suspicion,and at that point,diagnostic value of TI-RADS and ATA guidelines were nearly the same(sensitivity,93.1％vs 93.8％;specificity,97.9％ vs 96.9％;PPV,99.5％ vs 99.2％;NPV,75.7％vs 79.5％;and accuracy,94.0％vs94.4％),and there was no significant differences (P=0.50,P=0.50,P=0.50,P=0.53,P=0.55),Kappa=0.97.Conclusions Both TI-RADS and the ATA guidelinesprovide effective malignancy risk stratification for thyroid nodules.The diagnosticvalue of TI-RADS when considering ≥ 4c and ATA guidelines when considering ≥ high-suspicion nodules as malignant were nearly the same and both high.
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OBJECTIVE: To investigate the inhibition effects of Tianshen Yizhi Recipe (TSYZR), a compound traditional Chinese herbal medicine, on decreased expression of nicotinic acetylcholine receptor (nAChR) and the neurotoxicity as well as lipid peroxidation induced by beta-amyloid peptide (Abeta) in human SH-SY5Y neuroblastoma cells. METHODS: The SH-SY5Y cells were treated by a certain concentration of TSYZR, and then exposed to Abeta(25-35). Methyl thiazolyl tetrazolium reduction assay was carried out to understand the influences of the drugs on cellular viability. Expressions of nAChR subunits (alpha3 and alpha7) at protein and mRNA levels were detected by Western-blotting and reverse transcription polymerase chain reaction, respectively. Lipid peroxidation was measured by thiobarbituric acid to observe the capacity of antioxidant of the drugs. RESULTS: TSYZR at a safe concentration could increase alpha7 protein in the cells, inhibit decreased expressions of alpha3 and alpha7 nAChR subunit proteins, prevent lower expression of alpha7 mRNA in SH-SY5Y cells induced by Abeta, reduce the neurotoxicity and lipid peroxidation resulting from Abeta, but had no significant effect on the lower expression of alpha3 mRNA. CONCLUSIONS: TSYZR can up-regulate the expression of alpha7 nAChR subunit protein and prevent decreased expressions of nAChRs and neurotoxicity as well as lipid peroxidation induced by Abeta. This drug may play an important therapeutic role in treatment of Alzheimer disease.