Clinical characteristics of acute myeloid leukaemia patients with a large number of azurophilic granules: A single-centre retrospective study.

Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D-dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3-ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.

Deubiquitinase OTUD5 promotes hepatitis B virus replication by removing K48-linked ubiquitination of HBV core/precore and upregulates HNF4ɑ expressions by inhibiting the ERK1/2/mitogen-activated protein kinase pathway.

Hepatitis B virus (HBV) infection is a major public health problem worldwide, causing nearly one million deaths annually. OTUD5 is a deubiquitinase associated with cancer development and innate immunity response. However, the regulatory mechanisms of OTUD5 underlying HBV replication need to be deeply elucidated. In the present investigation, we found that HBV induced significant up-regulation of OTUD5 protein in HBV-infected cells. Further study showed that OTUD5 interacted with HBV core/precore, removing their K48-linked ubiquitination chains and protecting their stability. Meanwhile, overexpression of OTUD5 could inhibit the MAPK pathway and then increase the expression of HNF4ɑ, and ERK1/2 signaling was required for OTUD5-mediated activation of HNF4α, promoting HBV replication. Together, these data indicate that OTUD5 could deubiquitinate HBV core protein degradation by its deubiquitinase function and promote HBV activity by up-regulating HNF4α expression via inhibition of the ERK1/2 pathway. These results might present a novel therapeutic strategy against HBV infection.

HBcrAg and pg RNA and the therapeutic effect in HBeAg-positive patients receiving anti-viral therapy, baseline serum HBV-RNA is a powerful predictor of response.

We used HBV core antigen (HbcrAg), pre-genomic RNA (pg RNA) and other biomarkers to evaluate the therapeutic effect in HBV infected patients receiving anti-viral therapy. 127HBeAg-positive patients were enrolled: 35 patients received nucleotide therapy, 14 patients received interferon and 78 patients received combination therapy with both. HBcrAg, pg RNA and other biomarkers were detected at different time points, we defined the decreased titre of HBcrAg and HBeAg from baseline to 6 and baseline to 12 months as ∆HBcrAg and ∆HBeAg, which were used to predict HBeAg seroconversion. Furthermore, we used the time-dependent receiver operator curve of different markers to analyse HBeAg seroconversion. For HBeAg seroconversion: at 6 months, 0.75 log10 U/mL of ∆HBcrAg and 1.47 log10 PEI U/mL of ∆HBeAg showed maximum predictive value in receiver operator curve analysis (Youden's index values for area under the curve of 0.687 and 0.646, respectively). At 12 months, 2.05 log10 U/mL of ∆HBcrAg and 1.92 log10 PEI U/mL of ∆HBeAg showed improved prediction (maximum Youden's index values, with areas under the curve of 0.688 and 0.698, respectively).pg RNA was a better predictor of outcome due and the concentrations of 6.20 log10 I U/mL of pg RNA and 8.0 log10 U/mL of HBcrAg were cut-off values for response in a Kaplan-Meier curve analysis. Our results may be used to identify the pg RNA concentration in patients at baseline and ∆HBcrAg during therapy who are likely to achieve HBeAg seroconversion according to the cut-off value at different time points, thus helping to evaluate the therapeutic effect.

Role of Aspergillus fumigatus-Specific IgE in the Diagnosis of Allergic Bronchopulmonary Aspergillosis.

INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) has been regarded as a rare disease in China due to the lack of quantitative detection of Aspergillus fumigatus-specific IgE (sIgE). We compared the diagnostic rate of ABPA among asthma patients with or without A. fumigatus-sIgE screening tests to evaluate the benefit of the tests in diagnosing ABPA. METHODS: We reviewed the detection rate of A. fumigatus-sIgE and the diagnostic rate of ABPA in 1842 asthma patients in the First Affiliated Hospital of Zhejiang University from 2014 to 2016. Additionally, we collected 144 asthma cases from November 2016 to March 2017 to detect the total serum IgE, A. fumigatus-sIgE and sIgE against mixed mold extract, the ABPA diagnostic rate of these patients was then compared with the total cohort. Total serum IgE, A. fumigatus-sIgE and sIgE against mixed mold extract were also tested in 30 patients identified with Aspergillus-positive sputum culture to analyze the incidence of ABPA. RESULTS: Among the 1,842 asthma cases, 566 were inspected for total IgE; 308 (55.40%) were total IgE-positive and 58 (10.43%) had total IgE > 1,000 IU/mL. In contrast, only 126 cases were tested for A. fumigatus-sIgE (6.84%), and 28 had A. fumigatus-sIgE > 0.35 kUA/L (22.22%). Eleven patients were finally diagnosed with ABPA. Of 1,842 asthma patients, only 0.6% were diagnosed with ABPA if the A. fumigatus-sIgE was not detected at first. Moreover, among the 144 asthma cases that were selected for total IgE, A. fumigatus-sIgE, and sIgE against mixed mold extract screening tests, 12 had total IgE > 1,000 IU/mL (8.33%), 11 had A. fumigatus-sIgE > 0.35 kUA/L (7.64%), and 14 had sIgE against mixed mold extract > 0.35 (9.72%); 7 of these patients were confirmed as having ABPA according to the ISHAM guidelines (4.86%) but only 2 without A. fumigatus-sIgE screening test were diagnosed with ABPA (1.39%) (p = 0.000). Of the 30 Aspergillus-positive sputum culture cases, 4 had A. fumigatus-sIgE > 0.35 kUA/L (13.33%), but none was diagnosed with ABPA. CONCLUSIONS: Routine A. fumigatus-sIgE screening for asthma patients can significantly improve the diagnostic rate of ABPA.

Baseline Quantitative Hepatitis B Core Antibody Titer Is a Predictor for Hepatitis B Virus Infection Recurrence After Orthotopic Liver Transplantation.

Objective: Hepatitis B virus (HBV) reinfection is a serious complication that arise in patients who undergo hepatitis B virus related liver transplantation. We aimed to use biomarkers to evaluate the HBV reinfection in patients after orthotopic liver transplantation. Methods: Seventy-nine patients who underwent liver transplantation between 2009 and 2015 were enrolled, and levels of biomarkers were analyzed at different time points. Cox regression and receiver operating characteristic (ROC) curves of different markers at baseline were used to analyze sustained hepatitis B surface antigen (HBsAg) loss. The Kaplan-Meier method was used to compare the levels of the biomarkers. Results: Among the 79 patients, 42 sustained HBsAg loss with a median time of 65.2 months (12.0-114.5, IQR 19.5) after liver transplantation and 37 patients exhibited HBsAg recurrence with a median time of 8.8 (0.47-59.53, IQR 19.47) months. In the ROC curve analysis, at baseline, 4.25 log10 IU/mL qHBcAb and 2.82 log10 IU/mL qHBsAg showed the maximum Youden's index values with area under the curves (AUCs) of 0.685and 0.651, respectively. The Kaplan-Meier method indicated that qHBsAg and quantitative antibody against hepatitis B core antigen (qHBcAb) levels in the two groups were significantly different (p = 0.031 and 0.006, respectively). Furthermore, the Cox regression model confirmed the predictive ability of qHBcAb at baseline (AUC = 0.685). Conclusion: Lower pretransplantation qHBcAb is associated with HBV infection. The baseline concentration of qHBcAb is a promising predictor for the recurrence of HBV in patients undergoing liver transplantation and can be used to guide antiviral treatment for HBV infection.

HBcrAg, pg RNA and HBsAg dynamically supervise the seroconversion of HBsAg with anti-viral therapy: "Loss of HBsAg" maybe not a good end-point of anti-viral therapy.

OBJECTIVE: We aimed to identify predictor of HBsAg seroconversion using serum quantitative pg-RNA, HBcrAg and HBsAg in CHB patients with anti-viral therapy. METHOD: A total of 335 patients with anti-viral therapy between 2013 and 2017 were enrolled, only 23 achieved the seroconversion of HBsAg, other 138 patients without seroconversion of HBsAg were selected randomly in 312 patients. The samples date of 161 patients were analyzed at different time. We defined the decrease titer of pg-RNA, HBcrAg and HBsAg from baseline to 6 months and baseline to 12 months as Δpg-RNA, ΔHBcrAg and ΔHBsAg, then we used the Δpg-RNA, ΔHBcrAg and ΔHBsAg to predict HBsAg seroconversion. RESULT: About 6.9% of patients achieved HBsAg seroconversion after a median of 3.61 years' treatment. Using ROC to predict seroconversion of HBsAg, ΔHBsAg of 0.64 log10 IU/mL with AUC of 0.886 (0.802, 0.969; 95% CI) at 6 months and ΔHBsAg of 1.45 log10 IU/mL with AUC of 0.939 (0.868, 1.000; 95% CI) at 12 months had the maximized Youden's index. The comparison of HBcrAg "conversion" rates using Kaplan-Meier method between 23 patients with HBsAg conversion and 138 patients with HBsAg no conversion indicated that the two groups had significant difference at the time of antiviral discontinuation (p = 0.0124). CONCLUSION: According to our results, we can use ΔHBsAg to pick out the appropriate patients who have the potential to achieve seroconversion by sticking to antiviral therapy, that is very important to reach the target of functional cure or even clinical cure.