In this study,we developed a novel on-line solid phase extraction(SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)-based analytical method for simultaneously quantifying 12 illic...In this study,we developed a novel on-line solid phase extraction(SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)-based analytical method for simultaneously quantifying 12 illicit drugs and metabolites(methamphetamine,amphetamine,morphine,codeine,6-monoacetylmorphine,benzoylecgonine,3,4-methylenedioxymethamphetamine,3,4-methylenedioxyamphetamine,cocaine,ketamine,norketamine,and methcathinone)and cotinine(COT)in wastewater samples.The analysis was performed by loading 2 m L of the sample onto an Oasis hydrophilic-lipophilic balance cartridge and using a cleanup step(5%methanol)to eliminate interference with a total run time of 13 min.The isotope-labeled internal standard method was used to quantify the target substances and correct for unavoidable losses and matrix effects during the on-line SPE process.Typical analytical characteristics used for method validation were sensitivity,linearity,precision,repeatability,recovery,and matrix effects.The limit of detection(LOD)and limit of quantification(LOQ)of each target were set at 0.20 ng/L and 0.50 ng/L,respectively.The linearity was between 0.5 ng/L and250 ng/L,except for that of COT.The intra-and inter-day precisions were<10.45%and 25.64%,respectively,and the relative recovery ranged from 83.74%to 162.26%.The method was used to analyze various wastewater samples from 33 cities in China,and the results were compared with the experimental results of identical samples analyzed using off-line SPE.The difference rate was between 19.91%and-20.44%,and the error range could be considered acceptable.These findings showed that on-line SPE is a suitable alternative to off-line SPE for the analysis of illicit drugs in samples.展开更多
This study aimed to investigate the prevalence,clinical characteristics,and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM).A retrospective analysis was conducted on 411 pat...This study aimed to investigate the prevalence,clinical characteristics,and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM).A retrospective analysis was conducted on 411 patients with newly diagnosed MM;among which,270 received bortezomib-based therapies,and 141 received thalidomide-based therapies.Fluorescence in situ hybridization (FISH) was performed to detect six cytogenetic abnormalities,namely,del(1p32.3),gain(1q21),del(17p13),del(13q14),t(4;14),and t(11;14).Results showed that 8.3% of patients with MM were detected with del(1p32.3) and had significantly more bone marrow plasma cells (P =0.025),higher β2-microglobulin levels (P =0.036),and higher lactate dehydrogenase levels (P =0.042) than those without del(1p32.3).Univariate analysis showed that patients with del(1p32.3) under thalidomide-based therapies were strongly associated with short progression-free survival (PFS) (median PFS 11.6 vs.31.2 months,P =0.002) and overall survival (OS) (median OS 16.8 vs.45.9 months,P < 0.001).Multivariate analysis revealed that del(1p32.3) remained a powerful independent factor with worse PFS (P =0.006) and OS (P =0.016) for patients under thalidomide-based treatments.Patients with del(1 p32.3) under bortezomib-based treatments tended to have short PFS and OS.In conclusion,del(1p32.3) is associated with short PFS and OS in patients with MM who received thalidomide-or bortezomib-based treatments.展开更多
A CALLG2008 protocol was developed by the Chinese Acute Lymphoblastic Leukemia Cooperative Group for adult acute lymphoblastic leukemia （ALL）. We retrospectively analyzed 153 newly diagnosed adult patients with Phil...A CALLG2008 protocol was developed by the Chinese Acute Lymphoblastic Leukemia Cooperative Group for adult acute lymphoblastic leukemia （ALL）. We retrospectively analyzed 153 newly diagnosed adult patients with Philadelphia chromosome （Ph）-positive ALL enrolled into imatinib （400 mg/d） plus CALLG2008 regimen between 2009 and 2015. The median age was 40 years （range, 18-68 years）, with 81 （52.3%） males. The overall hematologic complete remission （CR） rate was 96.7% after induction. With a median follow-up of 24.2 months, the estimated 3-year overall survival （OS） and event-free survival （EFS） rates were 49.5% （95% confidence interval （CI）： 38.5%-59.5%） and 49.2% （95% CI： 38.3%-59.2%）, respectively. Fifty-eight （36 with haploidentical donor） patients underwent allogeneic hematopoietic stem call transplantation （allo-HSCT） in first CR. Among the patients in CR1 after induction, both the 3-year OS and EFS were significantly better in the allo-HSCT group than in the without alIo-HSCT group （73.2%, 95% CI： 58.3%-83.5% vs. 22.2%, 95% CI： 8.7%-39.6% and 66.5%, 95% CI： 50.7%-78.2% vs. 16.1%, 95% CI： 5.1%-32.7%, respectively）. Multivariate analysis showed that alIo-HSCT and achievement of major molecular response were associated with favorable OS or EFS independently. Interestingly, in the alIo-HSCT cohort, the donor type （haploidentical versus matched donors） had no significant impact on EFS or OS. All these results suggested that imatinib plus CALLG2008 was an effective protocol for Ph-positive ALL. Haploidentical donors can also be a reasonable alternative expedient donor pool.展开更多
Acquired thrombotic thrombocytopenic purpura （TTP） is a rare life-threatening thrombotic microangiopathy. This study aimed to provide a profile of the diagnosis and management of patients with acquired TTP collected...Acquired thrombotic thrombocytopenic purpura （TTP） is a rare life-threatening thrombotic microangiopathy. This study aimed to provide a profile of the diagnosis and management of patients with acquired TTP collected in 10 years in a single center in southeast China. A total of 60 patients diagnosed with acute acquired TTP from March 2005 to August 2015 were enrolled. Among the 60 patients, 52 patients presented with their first episodes, and eight patients had two or more episodes. The median age at presentation was 49 （range, 17 to 78） years with a female predominance （male：female ratio, 1：1.60）. ADAMTS 13 activity were analyzed in 43 patients, among whom 33 （76.7%） patients had a baseline level of 〈 5%. Mortality was 30%. Plasma exchange （PEX） was performed in 62 of 69 （89.9%） episodes. Corticosteroids were administered in 54 of 69 （78.3%） episodes. Other immunosuppressants （e.g., vincristine, cyclosporine, and cyclosporin） were used in 7 of 69 （10.1%） episodes. Rituximab was documented in 4 patients with refractory/relapsed TTP for 5 episodes, showing encouraging results. In conclusion, the diagnosis of TTP depended on a comprehensive analysis of clinical data. Plasma ADAMTS13 activity assay helped confirm a diagnosis. PEX was the mainstay of the therapy, and rituximab can be used in relapsed/refractory disease.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.:2018YFC0807402)the National Natural Science Foundation of China(Grant No.:82073810)。
文摘In this study,we developed a novel on-line solid phase extraction(SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)-based analytical method for simultaneously quantifying 12 illicit drugs and metabolites(methamphetamine,amphetamine,morphine,codeine,6-monoacetylmorphine,benzoylecgonine,3,4-methylenedioxymethamphetamine,3,4-methylenedioxyamphetamine,cocaine,ketamine,norketamine,and methcathinone)and cotinine(COT)in wastewater samples.The analysis was performed by loading 2 m L of the sample onto an Oasis hydrophilic-lipophilic balance cartridge and using a cleanup step(5%methanol)to eliminate interference with a total run time of 13 min.The isotope-labeled internal standard method was used to quantify the target substances and correct for unavoidable losses and matrix effects during the on-line SPE process.Typical analytical characteristics used for method validation were sensitivity,linearity,precision,repeatability,recovery,and matrix effects.The limit of detection(LOD)and limit of quantification(LOQ)of each target were set at 0.20 ng/L and 0.50 ng/L,respectively.The linearity was between 0.5 ng/L and250 ng/L,except for that of COT.The intra-and inter-day precisions were<10.45%and 25.64%,respectively,and the relative recovery ranged from 83.74%to 162.26%.The method was used to analyze various wastewater samples from 33 cities in China,and the results were compared with the experimental results of identical samples analyzed using off-line SPE.The difference rate was between 19.91%and-20.44%,and the error range could be considered acceptable.These findings showed that on-line SPE is a suitable alternative to off-line SPE for the analysis of illicit drugs in samples.
基金We would like to thank the patients who donated multiple myeloma specimens.This work was partially supported by the National Natural Science Foundation of China(Nos.81400080 and 81470305)Leukemia Research Innovation Team of Zhejiang Province(No.2011R50015).
文摘This study aimed to investigate the prevalence,clinical characteristics,and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM).A retrospective analysis was conducted on 411 patients with newly diagnosed MM;among which,270 received bortezomib-based therapies,and 141 received thalidomide-based therapies.Fluorescence in situ hybridization (FISH) was performed to detect six cytogenetic abnormalities,namely,del(1p32.3),gain(1q21),del(17p13),del(13q14),t(4;14),and t(11;14).Results showed that 8.3% of patients with MM were detected with del(1p32.3) and had significantly more bone marrow plasma cells (P =0.025),higher β2-microglobulin levels (P =0.036),and higher lactate dehydrogenase levels (P =0.042) than those without del(1p32.3).Univariate analysis showed that patients with del(1p32.3) under thalidomide-based therapies were strongly associated with short progression-free survival (PFS) (median PFS 11.6 vs.31.2 months,P =0.002) and overall survival (OS) (median OS 16.8 vs.45.9 months,P < 0.001).Multivariate analysis revealed that del(1p32.3) remained a powerful independent factor with worse PFS (P =0.006) and OS (P =0.016) for patients under thalidomide-based treatments.Patients with del(1 p32.3) under bortezomib-based treatments tended to have short PFS and OS.In conclusion,del(1p32.3) is associated with short PFS and OS in patients with MM who received thalidomide-or bortezomib-based treatments.
文摘A CALLG2008 protocol was developed by the Chinese Acute Lymphoblastic Leukemia Cooperative Group for adult acute lymphoblastic leukemia （ALL）. We retrospectively analyzed 153 newly diagnosed adult patients with Philadelphia chromosome （Ph）-positive ALL enrolled into imatinib （400 mg/d） plus CALLG2008 regimen between 2009 and 2015. The median age was 40 years （range, 18-68 years）, with 81 （52.3%） males. The overall hematologic complete remission （CR） rate was 96.7% after induction. With a median follow-up of 24.2 months, the estimated 3-year overall survival （OS） and event-free survival （EFS） rates were 49.5% （95% confidence interval （CI）： 38.5%-59.5%） and 49.2% （95% CI： 38.3%-59.2%）, respectively. Fifty-eight （36 with haploidentical donor） patients underwent allogeneic hematopoietic stem call transplantation （allo-HSCT） in first CR. Among the patients in CR1 after induction, both the 3-year OS and EFS were significantly better in the allo-HSCT group than in the without alIo-HSCT group （73.2%, 95% CI： 58.3%-83.5% vs. 22.2%, 95% CI： 8.7%-39.6% and 66.5%, 95% CI： 50.7%-78.2% vs. 16.1%, 95% CI： 5.1%-32.7%, respectively）. Multivariate analysis showed that alIo-HSCT and achievement of major molecular response were associated with favorable OS or EFS independently. Interestingly, in the alIo-HSCT cohort, the donor type （haploidentical versus matched donors） had no significant impact on EFS or OS. All these results suggested that imatinib plus CALLG2008 was an effective protocol for Ph-positive ALL. Haploidentical donors can also be a reasonable alternative expedient donor pool.
文摘Acquired thrombotic thrombocytopenic purpura （TTP） is a rare life-threatening thrombotic microangiopathy. This study aimed to provide a profile of the diagnosis and management of patients with acquired TTP collected in 10 years in a single center in southeast China. A total of 60 patients diagnosed with acute acquired TTP from March 2005 to August 2015 were enrolled. Among the 60 patients, 52 patients presented with their first episodes, and eight patients had two or more episodes. The median age at presentation was 49 （range, 17 to 78） years with a female predominance （male：female ratio, 1：1.60）. ADAMTS 13 activity were analyzed in 43 patients, among whom 33 （76.7%） patients had a baseline level of 〈 5%. Mortality was 30%. Plasma exchange （PEX） was performed in 62 of 69 （89.9%） episodes. Corticosteroids were administered in 54 of 69 （78.3%） episodes. Other immunosuppressants （e.g., vincristine, cyclosporine, and cyclosporin） were used in 7 of 69 （10.1%） episodes. Rituximab was documented in 4 patients with refractory/relapsed TTP for 5 episodes, showing encouraging results. In conclusion, the diagnosis of TTP depended on a comprehensive analysis of clinical data. Plasma ADAMTS13 activity assay helped confirm a diagnosis. PEX was the mainstay of the therapy, and rituximab can be used in relapsed/refractory disease.
