[Clinical Characteristics and Risk Factors of Invasive Fungal Infections in Acute Leukemia Patients in Tropical Regions].

OBJECTIVE: To analyze the clinical characteristics and risk factors of invasive fungal infection (IFI) occurenced in patients with acute leukemia (AL) during treatment in tropical regions. METHODS: The clinical data of 68 AL patients admitted to the Hainan Hospital of PLA General Hospital from April 2012 to April 2019 was retrospectively analyzed. Logistic regression analysis was used to analyze the factors affecting the occurrence of IFI in AL patients. RESULTS: Among the 68 patients, 44 were acute myeloid leukemia, 24 were acute lymphoblastic leukemia, 39 were male, 29 were female and the median age was 41(13-75) years old. The 68 patients received 242 times of chemotherapy or hematopoietic stem cell transplantation(HSCT), including 73 times of initial chemotherapy or inducting chemotherapy after recurrence, 14 times of HSCT, 155 times of consolidating chemotherapy. Patients received 152 times of anti-fungal prophylaxis, including 77 times of primary anti-fungal prophylaxis and 75 times of secondary anti-fungal prophylaxis. Finally, the incidence of IFI was 31 times, including 24 times of probable diagnosis, 7 times of proven diagnosis, and the total incidence of IFI was 12.8%(31/242), the incidence of IFI in inducting chemotherapy was 24.66%(18/73), the incidence of IFI in HSCT patients was 28.57% (4/14), the incidence of IFI in consolidating chemotherapy was 5.80% (9/155). Multivariate analysis showed that inducting chemotherapy or HSCT, the time of agranulocytosis ≥7 days, risk stratification of high risk were the independent risk factors for IFI in AL patients during treatment in tropical regions. CONCLUSION: The incidence of IFI in patients with AL in the tropics regions is significantly higher than that in other regions at homeland and abroad. Anti-fungal prophylaxis should be given to the patients with AL who have the high risk factors of inducting chemotherapy or HSCT, time of agranulocytosis ≥7 days and risk stratification of high risk.

The effect of the detection of minimal residual disease for the prognosis and the choice of post-remission therapy of intermediate-risk acute myeloid leukemia without FLT3-ITD, NPM1 and biallelic CEBPA mutations.

BACKGROUND: Intermediate-risk acute myeloid leukemia (IR-AML) without FLT3-ITD, NPM1 and biallelic CEBPA mutations (here referred to as NPM1mut-negCEBPAdm-negFLT3-ITDneg AML) is a clinically heterogeneous disease. The optimal post-remission therapy (PRT) is unclear for patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML who achieved first complete response (CR1). This study aims to explore clinical and molecular factors that can help determine the prognosis of those patients and their choice of PRT. METHODS: We retrospectively analyzed 28 patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML who received induction chemotherapy and achieved CR1. For PRT, 17 patients received post-remission chemotherapy (PR-CT) and 11 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). RESULTS: For patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML, multivariate analysis indicated that allo-HSCT and negative minimal residual disease (MRDneg) before PRT were favorable prognostic factors of overall survival (OS) (allo-HSCT, P = 0.002; MRDneg, P = 0.018); whereas relapse was an adverse prognostic factor of OS (P = 0.003). Log-rank analysis showed that allo-HSCT significantly improved their OS and RFS compared with PR-CT (OS, P < 0.001; RFS, P = 001). Otherwise, allo-HSCT improved the OS and RFS of patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML, whether they obtained MRDpos or MRDneg before PRT (OS: MRDneg, P = 0.036; MRDpos, P = 0.012; RFS: MRDneg, P = 0.047; MRDpos, P = 0.030). CONCLUSION: For patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML, MRDneg before PRT and allo-HSCT were favorable prognostic factors of OS. Whether they obtain MRDneg or not, allo-HSCT is the preferred PRT.

[Single Center Analysis of Bloodstream Infection Clinical Characteristics and Prognosis in Patients with Hematological Malignancies in the Tropics].

OBJECTIVE: To analyze the characteristics, prognosis and risk factors of bloodstream infection in patients with hematological malignancies in the tropics, so as to provide evidence for the prevention and treatment of bloodstream infection. METHODS: The clinical features, blood culture results and prognosis of patients with bloodstream infection in patients with hematological malignancies admitted to Hainan Hospital of PLA General Hospital were retrospectively studied. RESULTS: The most common primary infection site of the 81 patients with hematological malignancies was lung (46.91%), followed by PICC (11.11%). The detection rate of Gram-positive bacteria and Gram-negative bacteria in the blood culture was 60.98% and 30.02%, respectively. Coagulase-negative staphylococci was the most common Gram-positive bacteria resulting in bloodstream infection in our study. Of the Gram-negatives, Klebsiella pneumoniae (34.38%) was predominant, followed by Escherichia coli (18.75%) and Pseudomonas aeruginosa (18.75%). Gram-positive bacteria was highly sensitive (100%) to vancomycin, linezolid and tigecycline. Study showed that Gram-negative bacteria had low sensitive to quinolones, in particular, the resistance rate of Escherichia coli to quinolones was as high as 83.33%. In terms of overall survival (OS), the 30-days OS of patients with Gram-negative and Gram-positive septicemia was 77.42% and 92.00%, respectively. There was no statistically significant difference between the two groups. Multivariate analysis revealed that septic shock (P=0.001, RR=269.27) was an independent risk factor for 30-day mortality, and remission status (P=0.027, RR=0.114) was an independent predictor of a favourable outcome of bloodstream infection in patients with hematological malignancies. CONCLUSION: Gram-positive bacteria are the main pathogens causing bloodstream infections in patients with hematological malignancies in the tropics. Improving the care of PICC is an important measure to reduce the incidence of bloodstream infection in patients with hematological malignancies in the tropics. A correct treatment relieving disease and effective prevention and treatment of septic shock can reduce mortality of patients with bloodstream infection in patients with hematological malignancies in the tropics.

[Clinical Characteristics and Prognosis of U2AF1 Mutation in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the incidence, clinical features of U2AF1 gene mutation in patients with acute myeloid leukemia(AML) and its effect of prognosis. METHODS: A total of 161 patients with AML were enrolled. The second-generation sequencing method was used to detect U2AF1 gene mutation, and the relationship between U2AF1 mutation and clinical features, prognosis was analyzed. RESULTS: The mutation rate of U2AF1 gene in 161 AML patients was 3.73%. The counts of peripheral blood leukocytes and platelets in the U2AF1 gene mutation group were lower than those in the wild type group. The complete response rate of U2AF1 gene mutation group was 66.67%, while that in wild type group was 55.48%, which shows no significant difference between the two groups (P=0.70). The median EFS of wild type group and the mutant group was not reached and reached to 133 days, respectively (P=0.03), while the medium OS in two groups was not reached and reached to 210 days (P=0.01). CONCLUSION: The AML patients with U2AF1 mutation positive have a poor prognosis as compared with the wild type group, which may be a poor prognostic factor for acute myeloid leukemia.

Human serum albumin templated MnO2 nanosheets are oxidase mimics for colorimetric determination of hydrogen peroxide and for enzymatic determination of glucose.

This paper reports on a colorimetric assay for H2O2 and glucose. It is based on the use of human serum albumin-templated MnO2 nanosheets that possess oxidase-like activity. They are capable of oxidizing 3,3',5,5'-tetramethylbenzidine (TMB) with oxygen to give a blue product (oxTMB) with an absorbance maximum at 652 nm. When H2O2 is introduced, the MnO2 nanosheets are reduced to Mn(II) ions, and this inhibits the formation of oxTMB. Based on these findings, a colorimetric assay was established for H2O2 that has a 0.56 µM detection limit. If glucose is oxidized by glucose oxidase under formation of H2O2, the nanosheets can be used to quantify H2O2 and thereby to sense glucose. Response is linear in the 0.5 µM to 50 µM glucose concentration range, and the detection limit is 0.32 µM. The method was applied to the determination of glucose in spiked serum samples and gave satisficatory results. Graphical abstract Human serum albumin (HSA) is used as a template for the synthesis of MnO2 nanosheet. These possess oxidase mimicking activity. H2O2 can reduce the nanosheets. The effect is exploited in colorimetric assays for H2O2 and glucose using tetramethylbenzidine (TMB) as a chromogenic substrate.

Fluorometric determination of nucleic acids based on the use of polydopamine nanotubes and target-induced strand displacement amplification.

The authors describe a fluorometric method for the quantitation of nucleic acids by combining (a) cycled strand displacement amplification, (b) the unique features of the DNA probe SYBR Green, and (c) polydopamine nanotubes. SYBR Green undergoes strong fluorescence enhancement upon intercalation into double-stranded DNA (dsDNA). The polydopamine nanotubes selectively adsorb single-stranded DNA (ssDNA) and molecular beacons. In the absence of target DNA, the molecular beacon, primer and SYBR Green are adsorbed on the surface of polydopamine nanotubes. This results in quenching of the fluorescence of SYBR Green, typically measured at excitation/emission wavelengths of 488/518 nm. Upon addition of analyte (target DNA) and polymerase, the stem of the molecular beacon is opened so that it can bind to the primer. This triggers target strand displacement polymerization, during which dsDNA is synthesized. The hybridized target is then displaced due to the strand displacement activity of the polymerase. The displaced target hybridizes with another molecular beacon. This triggers the next round of polymerization. Consequently, a large amount of dsDNA is formed which is detected by addition of SYBR Green. Thus, sensitive and selective fluorometric detection is realized. The fluorescent sensing strategy shows very good analytical performances towards DNA detection, such as a wide linear range from 0.05 to 25 nM with a low limit of detection of 20 pM. Graphical abstract Schematic of a fluorometric strategy for highly sensitive and selective determination of nucleic acids by combining strand displacement amplification and the unique features of SYBR Green I (SG) and polydopamine nanotubes.

A rapid fluorescence "switch-on" assay for glutathione detection by using carbon dots-MnO2 nanocomposites.

Glutathione (GSH) serves many cellular functions and plays crucial roles in human pathologies. Simple and sensitive sensors capable of detecting GSH would be useful tools to understand the mechanism of diseases. In this work, a rapid fluorescence "switch-on" assay was developed to detect trace amount of GSH based on carbon dots-MnO2 nanocomposites, which was fabricated through in situ synthesis of MnO2 nanosheets in carbon dots colloid solution. Due to the formation of carbon dots-MnO2 nanocomposites, fluorescence of carbon dots could be quenched efficiently by MnO2 nanosheeets through fluorescence resonance energy transfer (FRET). However, the presence of GSH would reduce MnO2 nanosheets to Mn(2+) ions and subsequently release carbon dots, which resulted in sufficient recovery of fluorescent signal. This proposed assay demonstrated highly selectivity toward GSH with a detection limit of 300nM. Moreover, this method has also shown sensitive responses to GSH in human serum samples, which indicated its great potential to be used in disease diagnosis. As no requirement of any further functionalization of these as-prepared nanomaterials, this sensing system shows remarkable advantages including very fast and simple, cost-effective as well as environmental-friendly, which suggest that this new strategy could serve as an efficient tool for analyzing GSH level in biosamples.