ABSTRACT
Methyl-diethanolamine (CAS: 105-59-9), ethyl-diethanolamine (CAS: 139-87-7), and triethanolamine (CAS: 102-71-6) were identified as the degradation products and bio-markers of nitrogen mustard exposure. Sensitive and convenient detection methods for amino alcohol are of great importance to identify nitrogen mustard exposure in forensic analysis. Herein, analytical methods including gas chromatography-tandem mass spectrometry combined with heptafluorobutyryl derivatization and solid phase extraction were established for retrospective detection of the biomarkers in human plasma and urine samples. The efficiency of the method was improved by optimizing the conditions for sample preparation and the GC-MS/MS method. The optimization included the derivatization temperature, reaction time, reagent dosage and solid phase extraction cartridges, eluent and pH of the loading sample. The results indicated that the SCX cartridge resulted in better enrichment and purification effects, and the best recovery could be obtained with pH = 3-4 for the loading samples and an eluent of 2 mL 10% NH4OH/MeOH. The GC-MS/MS parameters were also optimized for better specificity and sensitivity. The established method was fully validated for each analyte both in plasma and urine matrixes. The linear range of analytes in plasma was 1.0-1000 ng mL-1 with a correlation parameter (R2) of ≥0.994, intra-day/inter-day accuracy of 93.7-117%, and relative standard deviation (RSD) of ≤6.5%. Meanwhile the results in urine were 1.0-1000 ng mL-1 with R2 of ≥0.996, intra-day/inter-day accuracy of 94.3-122%, and RSD of ≤6.6%. The detection limit of the analytes was 1.0 ng mL-1. The method was applied for the detection and identification of trace amino alcohols present in urine samples dispatched by the Organization for the Prohibition of Chemical Weapons (OPCW) and the results were confirmed to be correct.
ABSTRACT
A simple, rapid and low-cost determination method of benzo(a)pyrene in fried and baked foods was proposed by high performance liquid chromatography combined with vesicular coacervative supramolecular solvent (SUPRAS) extraction. The vesicular coacervate was composed of 1-octanol and tetrabutylammonium bromide. 200 mg of dried samples with 600 µL SUPRAS could be mixed to extract benzo(a)pyrene. Neither evaporation nor further clean-up steps for the extracts were needed. The overall sample treatment took approximately 30 min, and several samples could be simultaneously treated using conventional lab equipment. Then, benzo(a)pyrene was analyzed via liquid chromatography-fluorescence detection. Parameters affecting the extraction efficiency were investigated and optimized. The results showed good linearity of benzo(a)pyrene with the coefficients of determination (R 2) of more than 0.9999 in the range of 0.1-50.0 µg/kg. The limit of detection of the method was 0.11 µg/kg. Recoveries for spiked samples in the range of 1-10 µg/kg were between 89.86 and 100.01%, with relative standard deviations from 1.20 to 3.20%. Benzo(a)pyrene was present in food samples (including instant noodles, biscuits, rice crust and fried bread stick) at concentrations in the range of 0.08-0.39 µg/kg according to the proposed method. The proposed pretreatment method significantly reduces the analysis time. Furthermore, the solventless approach is in accordance with the green chemistry development trend and has significant application prospects.
ABSTRACT
Objective: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL. Methods: The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without. Results: The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) . Conclusions: Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.
Subject(s)
Adult , Humans , Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cells, T-Lymphoid , Remission Induction , Retrospective StudiesABSTRACT
Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (Ctrough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers' group (30 cases) and poor metabolizers' group (35 cases). The Ctrough of the 65 patients were detected for 169 times totally, and there was a significant difference of Ctrough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of Ctrough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ2=11.689, P=0.020). Conclusion: Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their Ctrough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.
Subject(s)
Humans , Antifungal Agents , Cytochrome P-450 CYP2C19/genetics , Genotype , Hematologic Diseases/genetics , Mycoses , Phenotype , Polymorphism, Genetic , VoriconazoleABSTRACT
Objective To explore the infection status and clinical characteristics of healthcare-associated infection (HAD in patients initially diagnosed with multiple myeloma(MM) during the induction period.Methods Clinical data of 116 patients diagnosed with MM and initially treated with PAD(bortezomib + adriamycin + dexamethasone)or PDD(bortezomib + liposome doxorubicin + dexamethasone) regimen in a hospital were collected,infection rates and clinical characteristics of patients during the induction therapy period were analyzed statistically.Results Among 116 patients,69 received PAD regimen,and 47 received PDD regimen,infection rates in two groups were 79.7％ and 89.4％ respectively;73 patients received subcutaneous injection of bortezomib,43 received intravenous injection of bortezomib,infection rates in subcutaneous injection group and intravenous injection group were 78.1％ and 93.0％ respectively,difference was statistically significant between two groups(P＜0.05).During the induction period,HAI rate was 83.6％ (n =97),81 patients developed infection during the first course,infection status of 3 patients were not clear due to therapy outside the hospital,the actual infection rate was 71.7 ％ (81/113);infection rate during the second course was 56.6 ％ (64/113);a total of 98 patients completed three therapy courses,infection rate was 43.9％ (43/98);66 patients completed four therapy courses,infection rate was 28.8％ (19/66).With the increase of the therapy course,infection rate showed a downward trend.Infection sites from high to low were respiratory system,skin and mucosa,oral and gastrointestinal system,bloodstream,and urinary tract.Difference in constitute of clinical diagnosis between patients receiving and without receiving prophylactic antifungal agents during chemotherapy period was not statistically significant (P =0.063).Conclusion Infection rate is very high during induction period,the main infection site is respiratory system,clinicians and patients need to pay more attention to the prevention and treatment of respiratory system infection.
ABSTRACT
A Rhodamine-based dual chemosensor L1 for simultaneously detecting Fe3+ and Cu2+ was designed and synthesized. The spectroscopic properties of L1 were analyzed, and its recognition mechanism was speculated. We found that the addition of Fe3+ induced a great fluorescence enhancement, while Cu2+ induced a strong UV-Vis absorption enhancement. The results revealed that L1 was highly selective for recognizing Fe3+ and Cu2+ in UV-Vis spectroscopy in CH3OH-H2O (1/1, v/v, pH 7.2) with the interference of other metal ions. A good linear relationship between the fluorescence intensities of L1 and the concentration of Fe3+, as well as the UV-Vis absorption intensities of L1 and the concentration of Cu2+ was observed, respectively. The detection limit was 9.2 × 10-8 M (5.5 µg/L) for Fe3+ and 3.8 × 10-8 M (2.4 µg/L) for Cu2+, respectively. The detection capacity for targeted metal ions of Fe3+ and Cu2+ were studied, which are less than 5 min. Job's plot method for L1 with Fe3+ and ESI-MS for L1 with Cu2+ indicated a 1:1 stoichiometry in the complex. The results may provide an effective strategy for the design of new dual chemosensors for the rapid detection of targeted metal ions.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the efficacy and safety of subcutaneous injection of bortezomib in the treatment of de novo multiple myeloma (MM) patients.</p><p><b>METHODS</b>A total of 36 MM patients treated with bortezomib, adriamycin and dexamethasone (PAD) from January 2012 to April 2013 were analyzed. Among them, 18 received improved PAD (improved PAD group) with the subcutaneous injection of bortezomib, another 18 received conventional PAD (PAD group). The efficacy and safety of two groups were analyzed.</p><p><b>RESULTS</b>Except 4 cases can not be assessed, 32 patients were evaluated. Of 32 cases, 19(59.4%) achieved complete remission (CR) or very good partial remission (VGPR) after induction therapy, which were 61.1% and 57.1% for PAD group and improved PAD group, respectively (P=1.000). No significant difference between the time to achieve maximum effectiveness in two groups was detected. In the PAD group, one patient (5.6%) died of serious lung infection and eight (44.4%) experienced grade 3 or higher adverse events, while only one (5.6%) discontinued treatment in improved PAD group due to similar toxicity. Compared to PAD group, grade 3 or worse adverse events was significantly reduced in improved PAD group, the most common symptoms were leucopenia (33.3% vs 61.1%, P=0.086), thrombocytopenia (50.0% vs 61.1%), anaemia (27.8% vs 16.7%), infection (16.7% vs 50.0%, P=0.075), diarrhea (5.6% vs 33.3%, P=0.088), peripheral neuropathy(0 vs 27.8%, P=0.045).</p><p><b>CONCLUSION</b>The improved PAD regimen by changing bortezomib from intravenous administration to subcutaneous injection significantly reduced adverse events, improved the safety of clinical application of bortezomib without affecting curative effect, and had great progress.</p>
Subject(s)
Humans , Boronic Acids , Bortezomib , Dexamethasone , Doxorubicin , Injections, Subcutaneous , Multiple Myeloma , Drug Therapy , Pyrazines , Remission InductionABSTRACT
<p><b>OBJECTIVE</b>To report a case with pulmonary disease caused by nontuberculous mycobacteria (NTM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a literature review.</p><p><b>METHODS</b>Case report and literature review.</p><p><b>RESULTS</b>A patient with acute non-lymphocytic leukemia was treated by allo-HSCT. Her NTM lung disease developed after HSCT was successfully treated with a 3 antimicrobials combination of clarithromycin, levofloxacin and capreomycin for 10 months.</p><p><b>CONCLUSION</b>NTM infections are infrequent in allo-HSCT recipients and have a good clinical prognosis if correctly treated.</p>
