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In this study, we investigated whether matched and mismatched multidrug resistance gene (MDR1) genotypes (G2677TA, C1236T and C3435T) were associated with prognosis in patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). One hundred patients after transplantation and their donors were enrolled. Matched MDR1 G2677TA donor-recipient was associated with an increased risk of non-relapse mortality (NRM) (29.5% vs. 6.2%, p = 0.002), poor overall survival (OS) (51.7% vs. 63.8%, p = 0.024) and disease-free survival (DFS) (38.6% vs. 67%, p = 0.005). There were no differences in OS, DFS or NRM between MDR1 C1236T- and C3435T-matched and -mismatched groups. Subgroup analysis suggested that within the matched MDR1 G2677TA group, male gender, haematopoietic cell transplantation-specific comorbidity index ≥1, serum creatinine >137.2 µmol/L and post-transplantation thrombocytopenia were associated with poor survival. Our results demonstrated that patients receiving matched MDR1 G2677TA allo-HSCT experienced a poorer prognosis compared with the mismatched group. The potential mechanism may involve increased expression of P-glycoprotein, leading to decreased accumulation of antimicrobial agents and ultimately contributing to the progression of inflammation. This identification of MDR1 G2677TA genotype compatibility holds promise as a valuable molecular tool for selecting donors for allo-HSCT.
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Subfamília B de Transportador de Cassetes de Ligação de ATP , Genótipo , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Feminino , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Polimorfismo de Nucleotídeo Único , Doadores de Tecidos , Transplante Homólogo , Prognóstico , Idoso , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze the correlation between the mutational status of immunoglobulin heavy chain variable (IGHV) gene with the prognosis of patients with Waldenström macroglobulinemia (WM). METHODS: Immunoglobulin heavy chain gene (IGH) clonotypic sequence analysis was carried out to assess the mutational status of IGHV in the blood and/or bone marrow samples from 44 WM patients. The usage characteristics of IGHV-IGHD-IGHJ gene was explored. RESULTS: The most common IGHV subgroup was IGHV3, which was similar to the data from the Institute of Hematology of Chinese Academy of Medical Science. IGHV3-23 (20.45% vs. 15.44%) and IGHV3-74 (11.36% vs. 7.35%) were the main fragments used, which was followed by IGHV4 gene family (15.91% vs. 24.26%). However, no significant correlation was found between the IGHV4 usage and the prognosis of the patients. Should 98% be taken as the cut-off value for the IGHV mutation status, only 5 patients had no IGHV variant, and there was no correlation with the prognosis. Based on the X-tile analysis, 92.6% was re-selected as the cut-off value for the IGHV variant status in such patients. LDH was increased in 26 patients (59.1%) without IGHV variant (P < 0.05), whilst progression-free survival (P < 0.05) and overall survival (P < 0.05) were significantly shorter compared with those with IGHV variants. CONCLUSION: The usage characteristics of IGHV-IGHD-IGHJ in our patients was similar to reported by the Institute of Hematology of Chinese Academy of Medical Science, albeit that no correlation was found between the IGHV4 usage and the prognosis of the patients. Furthermore, 98% may not be appropriate for distinguishing the IGHV variant status in WM patients.
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Cadeias Pesadas de Imunoglobulinas , Macroglobulinemia de Waldenstrom , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Família Multigênica , Mutação , Macroglobulinemia de Waldenstrom/genéticaRESUMO
Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL.
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Síndromes do Eutireóideo Doente/sangue , Síndromes do Eutireóideo Doente/complicações , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/mortalidade , Tri-Iodotironina/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Tiroxina/sangueRESUMO
This study was performed to evaluate the variable indicators of polycyclic aromatic hydrocarbons (PAHs) source apportionment by using an unsteady-state multimedia model. The identical indicators have been used in different environmental bulks for more than 20 years, which resulted in huge errors in source apportionment. Generated through four emission arrays, the diagnostic ratios for indicators revealed dimensionless OR, in air/soil and seawater/sediment reached â¼3.63 and â¼0.24 for Fla/Pyr, and for Ant/Phe the ratio was â¼0.31 and â¼0.18, and coastal OR for air/seawater was higher than the offshore, suggesting both compartmental and spatial divergences. The PCA indicated similar loading distribution and primary factors, shared by emission, atmosphere, and seawater arrays, whereas the slow transport between air/water and soil/sediment, weak degradation, and original concentration level might result in factors in soil and sediment separated or merged in dynamic conditions. The physicochemical divergence of indicators could be intensified after long-term environmental transport, misleading the source apportionment. Therefore, the result elucidated the essential evaluation of additional inorganic indicators and necessary verification by simultaneous sampling measurement on vertical compartments.
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Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/análise , Multimídia , Monitoramento Ambiental/métodos , Água do Mar , Solo , ChinaRESUMO
Hydroponics combined with fugacity model was employed to investigate the kinetics of uptake, accumulation, and metabolism of organophosphate esters (OPEs) by japonica rice. The time-dependent process for uptake and accumulation of 5 OPEs and their diester-metabolites in both rice root and shoot fitted well with the pseudo-first-order kinetic model. The peak OPE accumulations in rice root and shoot were significantly positively or negatively correlated with their octanol-water partition coefficient (logKow) respectively, but not for their apparent accumulation rates. Root concentration factors (RCFs) and root-to-shoot translocation factors (TFs) of OPEs were found to be positively and negatively correlated with their logKow, respectively. Triphenyl phosphate with benzene ring substituents showed the highest RCF, but the lowest TF, because of its high potential for root adsorption due to the π electron-rich structures. Sterilized root exudates can hinder the root adsorption and absorption of OPEs from solution probably through competitive adsorption of OPEs with root surface. The first-hand transport and metabolism rates were also obtained by generating these rates to fit the dynamic fugacity model with the measurement values. The simulation indicated that the kinetics of OPE accumulation in rice plants may be controlled by multiple processes and physicochemical properties besides Kow.
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The target of this study was to reconstruct the historical concentration, distribution, variation, and exposure risk evaluation for EPA PAHs to the whole sea of Bohai Bay and the coastal population, by employing a specific dynamic multimedia model during 1950-2050. The unsteady-state model, driven by temporal energy activities from 1950 and sustainable scenarios based on socioeconomic development, indicated the annual emission increased by 4.6 times (from 84.8 tons to 391 tons) until 2020 and resulted in concentrations up to 5.2 times in the atmospheric compartment, and 4.9 times in seawater. Two peak concentrations in 1997 and 2014, consistent with total PAHs input revealed significant regional anthropogenic input in northern Bohai Bay (Tianjin) and southern Bohai Bay (Hebei). The peak-to-peak values of the timing concentration revealed a notably alternative increase in the south (+109.4 %-128.6 %), instead of the rapid decline in the north (-21.5 %-44.5 %). The dominant processes at air-seawater interfaces were air-seawater molecular transfer (from 38.4 % to 51.8 %), and wet deposition (from 60.5 % to 47.5 %). Under 5 shared socioeconomic pathways, the optimal scenario (SSP1) achieved a 24.7 % emission decline, an atmospheric decrease of 15.1 %-31.1 %, and 24.8 %-41.2 % mitigation in seawater during 2020-2050, and each pathway exhibited a general lessening concave in the northern developed municipality, compared with convex in the southern developing regions. The inhalation risk assessment evaluated 10 generations living on Bohai Bay coasts, with an acceptable result, while the current sustainable conceive was with meager fruition in reducing risk.
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Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Baías , Hidrocarbonetos Policíclicos Aromáticos/análise , Saúde Pública , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Água do Mar , ChinaRESUMO
OBJECTIVES: Refractory cytomegalovirus reactivation (RCR) after allo-hematopoietic stem cell transplantation (HSCT) is associated with poor outcomes. Current studies for the risk factors and survival of patients with post-transplantation RCR remain limited. METHODS: 163 patients with Cytomegalovirus (CMV) reactivation undergoing allo-HSCT in Jiangsu Province hospital from Jan 2013 to Dec 2020 were analyzed retrospectively. RESULTS: Multivariate analysis revealed that highest CMV viremia>1 × 104copies/mL (hazard ratio [HR] 16.895, 95% confidence interval [CI] 3.394-84.109, P = 0.001) and platelet count at Day 90 of more than 87.3 × 109/L (HR 0.381, 95% CI 0.154-0.945, P = 0.037) were independent risk factors affecting RCR. As for prognosis of patients with CMV reactivation, results showed that patients with RCR had higher risk of non-relapse mortality (NRM) (39.5% vs. 22.5%, P = 0.045), and RCR was an independent risk factor for NRM (HR 2.216, 95% CI 1.137-4.317, P = 0.019). There was no significance between patients with or without RCR in terms of overall survival (OS) (50.7% vs. 55.6%, P = 0.281) and relapse-free survival (RFS) (43.6% vs. 52.0%, P = 0.179). The landmark analysis showed that patients with RCR had higher NRM (P = 0.01), worse OS (P = 0.02), and RFS (P =0.01) within 100 days after transplantation. Patients with hemorrhagic cystitis (40.9% vs. 64.5%, P =0.028) and who developed viremia>1 × 105copies/mL (43.4% vs. 58.4%, P = 0.033) were associated with worse OS. CONCLUSION: Factors such as higher viral load, thrombocytopenia, and ATG used in conditioning therapy increased the incidence of RCR. Patients with RCR had worse NRM, OS, and RFS within 100 days after transplantation.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Citomegalovirus/fisiologia , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos , Viremia/etiologia , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Fatores de Risco , RecidivaRESUMO
BACKGROUND: Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a comprehensive model which could predict severe aGVHD after HID HSCT. METHODS: Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://clinicaltrials.gov (NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected as training cohort and the remains 30% (n = 135) were used as validation cohort. RESULTS: The equation was as follows: Probability (grade III-IV aGVHD) = [Formula: see text], where Y = -0.0288 × (age) + 0.7965 × (gender) + 0.8371 × (CD3 + /CD14 + cells ratio in graft) + 0.5829 × (donor/recipient relation) - 0.0089 × (CD8 + cell counts in graft) - 2.9046. The threshold of probability was 0.057392 which helped separate patients into high- and low-risk groups. The 100-day cumulative incidence of grade III-IV aGVHD in the low- and high-risk groups was 4.1% (95% CI 1.9-6.3%) versus 12.8% (95% CI 7.4-18.2%) (P = 0.001), 3.2% (95% CI 1.2-5.1%) versus 10.6% (95% CI 4.7-16.5%) (P = 0.006), and 6.1% (95% CI 1.3-10.9%) versus 19.4% (95% CI 6.3-32.5%) (P = 0.017), respectively, in total, training, and validation cohort. The rates of grade III-IV skin and gut aGVHD in high-risk group were both significantly higher than those of low-risk group. This model could also predict grade II-IV and grade I-IV aGVHD. CONCLUSIONS: We established a model which could predict the development of severe aGVHD in HID HSCT recipients.
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The study investigated pretreatment Epstein-Barr virus (EBV) DNA status and its prognostic values in 96 patients newly diagnosed Hodgkin lymphoma (HL). With 13.5 % patients in positive EBV DNA status before therapy, the positive group had inferior progression-free survival (PFS) (P = 0.023) as well as overall survival (OS) (P = 0.001). Pretreatment EBV DNA positivity was observed as an independent prognostic factor in OS (P = 0.036) while a trend to predict PFS (P = 0.064). By monitoring changes of EBV DNA copies in 13 patients with positive pretreatment EBV DNA status, 5 of 6 patients with complete response (CR) had their copies undetectable after 3 cycles of first-line treatment and 7 patients with progressive disease (PD) all had elevated EBV DNA copies during their relapsed period. Whole blood EBV DNA may be an adjunctive biomarker to reflect treatment response, risk of disease relapse as well as prognosis in HL patients.
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DNA Viral , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Doença de Hodgkin/sangue , Doença de Hodgkin/mortalidade , Carga Viral , Biomarcadores , Doença de Hodgkin/etiologia , Doença de Hodgkin/terapia , Humanos , PrognósticoRESUMO
The study investigated serum 25-Hydroxy vitamin D (25-(OH)D) deficiency and its prognostic values of patients newly diagnosed Hodgkin lymphoma (HL). With seventy-seven patients enrolled, the median level of 25-(OH)D was 44.5 nmol/L (range, 15.5-100.9 nmol/L) and 16 (20.8 %) of them were considered as 25-(OH)D deficiency. With a median follow-up of 28 months (range, 4-56 months), the 2-year progression-free survival (PFS) and overall survival (OS) rate were 75.3 %±5.5 % and 94.7 %±3.0 %, respectively. Patients with deficient 25-(OH)D level had inferior PFS (P<0.001) as well as OS (P<0.001). In multivariate Cox analysis, 25-(OH)D deficiency was observed as an independent prognostic factor for both PFS (hazard ratio (HR) 3.323, 95 % CI 1.527-7.229, P = 0.002) and OS (HR 5.819, 95 % CI 1.322-25.622, P = 0.020). Receiver-operator characteristic (ROC) curve showed International Prognostic Score (IPS) plus 25-(OH)D deficiency (IPS-D) predicted more accurately than IPS in PFS (AUC: 0.735 (95 % CI 0.622-0.829) vs. 0.701 (95 % CI 0.586-0.800), P = 0.033) and OS (AUC: 0.864 (95 % CI 0.767-0.932) vs. 0.825 (95 % CI 0.722-0.902), P = 0.028). All these findings suggest that serum 25-(OH)D level may be an adjunctive indicator to predict prognosis in HL patient.
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Biomarcadores Tumorais/sangue , Doença de Hodgkin/sangue , Deficiência de Vitamina D/sangue , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto JovemRESUMO
Peripheral T-cell lymphomas, unspecified (PTCL-U) is a heterogeneous group of non-Hodgkin lymphomas, arising from the transformation of mature, post-thymic T-cells. Prognostic index for PTCL-U (PIT) is based on Europeans and may not be applicable for Chinese PTCL-U patients. Besides, low circulating cholesterol concentration is associated with elevated cancer incidence and mortality. The purpose of our study was to assess the prognostic value of serum lipid levels in PTCL-U and improve PIT. We screened the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) by multivariate Cox regression analysis in ninety-one enrolled patients. The results showed that low-level high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were associated with unfavorable OS. Furthermore, we developed a new risk model, PITC, based on low-level HDL-C, LDL-C and PIT. In Chinese PTCL-U, PITC was superior to PIT in PFS and OS. In conclusion, serum cholesterol levels may be good candidates for predicting prognosis in PTCL-U.
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HDL-Colesterol/sangue , LDL-Colesterol/sangue , Linfoma de Células T Periférico/sangue , Linfoma de Células T Periférico/mortalidade , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
In this study, polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), and dechlorane plus (DPs) were analyzed in seven categories of building and decoration materials. The total concentrations of analyzed FRs ranged from 1.19â¯ng/g (diatomite powder) to 9532â¯ng/g (expanded polystyrene panel). Relatively high concentrations were detected in foam samples and PVC materials, followed by sealing materials, boards, wallpaper, paints, and wall decoration powders. BDE209 was the most detected compound with the highest concentrations in almost all materials, followed by decabromodiphenyl ethane (DBDPE), which was consistent with their productions and consumptions in China. The estimated PBDE concentrations in air and dust based on material concentration and emission rate were comparable with those detected in real samples. Adult and infant exposures via inhalation and dust ingestion were assessed. The estimated exposures to BDE209 via dust ingestion were 1.36 and 0.12 ng/(kg bw d), which were 19- and 4-fold higher than those via inhalation for infants and adults, respectively. This suggested that dust ingestion was a significant pathway of human BDE209 exposure, especially for infants. For the other PBDE congeners (∑7PBDEs), the estimated exposures via inhalation were 2.60 and 1.32 ng/(kg bw d) for infants and adults, respectively. Despite the low estimated human exposures to PBDEs compared to the oral reference doses, the exposure associated with building and decoration materials still requires more attention because of the potential risks from other exposure pathways and undetected FRs in those materials.
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Poluição do Ar em Ambientes Fechados/análise , Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Hidrocarbonetos Clorados/análise , Compostos Policíclicos/análise , Adulto , China , Poeira/análise , Ingestão de Alimentos , Halogenação , Humanos , LactenteRESUMO
The diurnal atmospheric concentrations of polychlorinated biphenyls (PCBs) were investigated at an abandoned e-waste recycling site in South China during winter and summer. Total PCB concentrations during winter and summer were 27.6-212 and 368-1704pg/m3 in the particulate phase and 270-697 and 3000-15,500pg/m3 in the gaseous phase, respectively. Both gaseous and particulate PCB concentrations and compositions exhibited significant difference between winter and summer samples, but no diurnal variations during the measurement period. The correlation analysis between PCB concentrations and meteorological conditions, including atmospheric temperature, humidity, and mixing layer height, suggested that the seasonal variability of atmospheric PCB concentrations was strongly temperature-dependent, while the diurnal variability was probably source-dependent. The temperature-driven variations can also be proved by the significant linear correlation between ln P and 1/T in the Clausius-Clapeyron plot. Although government has implemented controls to reduce e-waste pollution, both the relatively high concentrations of PCBs and the diurnal variation in the air suggested that emissions from occasional e-waste recycling activities may still exist in this recycling area. These results underline the importance of continuing e-waste recycling site management long after abandonment.
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Poluentes Atmosféricos/análise , Resíduo Eletrônico , Monitoramento Ambiental , Bifenilos Policlorados/análise , Atmosfera , China , Reciclagem , Estações do AnoRESUMO
Epstein-Barr virus (EBV)-DNA is detected in the blood of some persons with chronic lymphocytic leukemia (CLL) at diagnosis. Whether this is important in the development or progression of CLL is controversial. We interrogated associations between blood EBV-DNA copy number and biological and clinical variables in 243 new-diagnosed consecutive subjects with CLL. Quantification of EBV-DNA copies was done by real-time quantitative PCR (RQ-PCR). All subjects had serological evidence of prior EBV-infection. However, only 24 subjects (10%) had a EBV-DNA-positive test at diagnosis. EBV-DNA-positive subjects at diagnosis had lower hemoglobin concentrations and platelet levels, higher thymidine kinase-1 and serum ferritin levels, un-mutated IGHV genes and a greater risk of Richter transformation compared with EBV-DNA-negative subjects. Percent CD20-, CD148- and ZAP70-positive cells and mean fluorescence intensity (MFI) of each cluster designation were also increased in EBV-DNA-positive subjects at diagnosis. EBV-DNA test positivity was associated with a briefer time-to-treatment interval (HR 1.85; [95% confidence interval, 1.13, 3.03]; P=0.014) and worse survival (HR 2.77; [1.18, 6.49]; P=0.019). Reduction in EBV copies was significantly associated with therapy-response. A positive blood EBV-DNA test at diagnosis and sequential testing of EBV copies during therapy were significantly associated with biological and clinical variables, time-to-treatment, therapy-response and survival. If validated these data may be added to CLL prognostic scoring systems.