Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 309
Filtrar
1.
Front Oncol ; 11: 750218, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790576

RESUMO

Twenty patients with relapsed B-ALL after HSCT were treated with CAR T cell therapy and were evaluated for efficacy and safety. Twelve patients previously received haploidentical transplantation, while 8 patients received HLA-matched transplantation. The median relapse time was 12 months (range, 4 to 72). Thirteen patients received autologous CAR T cells, and 7 patients received allogeneic CAR T cells, which were derived from transplant donors. The median infusion dose was 2.9×106/kg (range, 0.33 to 12×106/kg). Nineteen patients were evaluated for efficacy, among which 17 patients (89.5%) achieved MRD negative. The CR rates in the HLA-matched transplantation group and haploidentical transplantation group were 100% (7/7) and 83.3% (10/12), respectively. The median follow-up time was 9.80 months (range, 2.40 to 64.97). Ten patients (50%) died of relapse, 3 patients (15%) died of infection, and 1 patient (5%) died of aGVHD. Fifteen patients (75%) developed CRS, including 3 (20%) grade 1 CRS, 6 (40%) grade 2 CRS, and 6 (40%) grade 3 CRS. Ten patients (50%) developed aGVHD, including 1 (10%) grade I aGVHD, 6 (60%) grade II aGVHD, and 3 (30%) grade III aGVHD. The log rank test showed that CAR T cell origin was correlated with aGVHD occurrence in the haploidentical transplantation group (P = 0.005). The authors' study indicated that the initial efficacy and safety of CAR T cell therapy for patients with post-transplant relapse were satisfactory. However, aGVHD was a concern in patients with a history of haploidentical transplantation occupied with allogeneic CAR T cells, which warrants clinical attention.

2.
J Phys Chem Lett ; : 11488-11496, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793176

RESUMO

In this study, we present that 2D tetrahex-GeC2 materials possess novel electronic and carrier transport properties based on density functional theory computations combined with the nonequilibrium Green's function method. We show that under the 4% (-4%) in-plane expansion (compression) along the a-direction (b-direction) of the tetrahex-GeC2 monolayer, the bandgap can be enlarged to a desirable 1.26 eV (1.32 eV), close to that of silicon. The carrier transport properties of both the sub-10 nm tetrahex-GeC2 monolayer and the bilayer show strong anisotropy within the bias from -1 to 1 V. The current ON (a-direction)/OFF (b-direction) ratio amounts to 105 for the tetrahex-GeC2 monolayer. A striking negative differential conductance arises with the maximum Ipeak/Ivalley on the order of 104 under the 4% uniaxial expansion along the b-direction of the tetrahex-GeC2 monolayer. Overall, the 2D tetrahex-GeC2 monolayer and bilayer possess highly tunable electronic and carrier transport properties under uniaxial strain, which can be exploited for potential applications in nanoelectronics.

3.
Front Hum Neurosci ; 15: 777043, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744673

RESUMO

Introduction: Cognitive decline is the core schizophrenia symptom, which is now well accepted. Holding a role in various aspects of cognition, lentiform nucleus (putamen and globus pallidus) dysfunction contributes to the psychopathology of this disease. However, the effects of lentiform nucleus function on cognitive impairments in schizophrenia are yet to be investigated. Objectives: We aim to detect the fractional amplitude of low-frequency fluctuation (fALFF) alterations in patients with schizophrenia, and examine how their behavior correlates in relation to the cognitive impairments of the patients. Methods: All participants underwent magnetic resonance imaging (MRI) and cognitive assessment (digit span and digit symbol coding tests). Screening of brain regions with significant changes in fALFF values was based on analysis of the whole brain. The data were analyzed between Jun 2020 and Mar 2021. There were no interventions beyond the routine therapy determined by their clinicians on the basis of standard clinical practice. Results: There were 136 patients (75 men and 61 women, 24.1 ± 7.4 years old) and 146 healthy controls (82 men and 64 women, 24.2 ± 5.2 years old) involved in the experiments seriatim. Patients with schizophrenia exhibited decreased raw scores in cognitive tests (p < 0.001) and increased fALFF in the bilateral lentiform nuclei (left: 67 voxels; x = -24, y = -6, z = 3; peak t-value = 6.90; right: 16 voxels; x = 18, y = 0, z = 3; peak t-value = 6.36). The fALFF values in the bilateral lentiform nuclei were positively correlated with digit span-backward test scores (left: r = 0.193, p = 0.027; right: r = 0.190, p = 0.030), and the right lentiform nucleus was positively correlated with digit symbol coding scores (r = 0.209, p = 0.016). Conclusion: This study demonstrates that cognitive impairments in schizophrenia are associated with lentiform nucleus function as revealed by MRI, involving working memory and processing speed.

4.
Int J Gen Med ; 14: 5475-5481, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531675

RESUMO

Object: To evaluate the effects of ultrasound-guided fine-needle aspiration with or without negative pressure (FNA+P or FNA-P) on diagnosis of thyroid nodules. Methods: A prospective randomized study was performed. Patients (n=1374, female=1094, 79.6%, male=280, 20.4%, age=48.7±12.5 yr) with thyroid nodules were randomly divided into FNA-P (n=774, 56.3%) and FNA+P (600, 43.7%) groups. Thyroid nodules were diagnosed by FNA-P or FNA+P, in the left (n=640, 46.6%) and right (n=734, 53.4%). Results: The thyroid nodules were diagnosed as microcalcification (n=751, 54.7%), coarse calcification (n=404, 29.4%), peripheral calcification (n=101, 7.4%) and mixed micro + coarse calcification (n=118, 8.6%). Based on Bethesda classification criteria, the thyroid nodules were cataloged as type I (n=217,15.8%), II (n=467, 34.0%), III (n=151, 11.0%), V (n=333, 24.2%), and VI (n=206, 15.0%). There were no significant differences between experimental groups diagnosed by FNA-P or FNA+P. Conclusion: The results suggest that fine-needle aspiration with or without negative pressure does not significantly affect the sensitivity of thyroid nodule diagnosis.

6.
Chem Commun (Camb) ; 57(79): 10178-10181, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34523642

RESUMO

A flexible porous water-soluble supramolecular organic framework was developed, which could efficiently exhibit phosphorescence both in an aqueous phase and in a film state at room-temperature.

7.
J Agric Food Chem ; 69(39): 11572-11581, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34554742

RESUMO

A series of novel steroidal derivatives with a substituted 1,3,4-oxadiazole structure was designed and synthesized, and the target compounds were evaluated for their insecticidal activity against five aphid species. Most of the tested compounds exhibited potent insecticidal activity against Eriosoma lanigerum (Hausmann), Myzus persicae, and Aphis citricola. Compounds 20g and 24g displayed the highest activity against E. lanigerum, showing LC50 values of 27.6 and 30.4 µg/mL, respectively. Ultrastructural changes in the midgut cells of E. lanigerum were detected by transmission electron microscopy, indicating that these steroidal oxazole derivatives might exert their insecticidal activity by destroying the mitochondria and nuclear membranes in insect midgut cells. Furthermore, a field trial showed that compound 20g exhibited effects similar to those of the positive controls chlorpyrifos and thiamethoxam against E. lanigerum, reaching a control rate of 89.5% at a dose of 200 µg/mL after 21 days. We also investigated the hydrolysis and metabolism of the target compounds in E. lanigerum by assaying the activities of three insecticide-detoxifying enzymes. Compound 20g at 50 µg/mL exhibited inhibitory action on carboxylesterase similar to the known inhibitor triphenyl phosphate. The above results demonstrate the potential of these steroidal oxazole derivatives to be developed as novel pesticides.


Assuntos
Afídeos , Inseticidas , Praguicidas , Animais , Inseticidas/farmacologia , Oxidiazóis/farmacologia
8.
Clin Cancer Res ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548316

RESUMO

PURPOSE: B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy results in high remission rates in patients with relapsed/refractory (R/R) multiple myeloma. However, the factors associated with prognosis following CAR T-cell therapy are unknown. PATIENTS AND METHODS: Between July 1, 2018 and July 31, 2020, 61 patients with R/R multiple myeloma received anti-BCMA CAR T-cell therapy (Chictr.org number, ChiCTR1800017404). Step-wise multivariate Cox regression and competing risk analyses were conducted to identify poor prognosis-associated risk factors. RESULTS: Sixty patients (98.4%) experienced cytokine release syndrome (CRS), including 33, 23, and 4 cases of CRS grades 1 to 2, 3, and 4, respectively. The objective response rate (ORR) was 98.3%, and the complete remission (CR) rate was 70.3%. With a median follow-up period of 21.1 months, the 1-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 50.2%, respectively. The median PFS was 12.7 months. Cox modeling revealed that poor PFS was associated with extramedullary disease [HR = 2.59, 95% confidence interval (95% CI) = 1.29-5.21, P = 0.008], light chain multiple myeloma (HR = 2.53, 95% CI = 1.03-5.97, P = 0.035), high-risk cytogenetics (HR = 2.80, 95% CI = 1.27-6.14, P = 0.01), and prior treatment with more than 3 therapeutic lines (HR = 3.14, 95% CI = 1.34-7.34, P = 0.008). Among the 41 CR cases, competing risk analyses demonstrated higher relapse predispositions in those with extramedullary disease (HR = 4.51, 95% CI = 1.86-10.9, P = 0.001), light chain multiple myeloma (HR = 4.89, 95% CI = 1.52 - 15.7, P = 0.008), or high-risk cytogenetics (HR = 5.09, 95% CI = 1.63-15.9, P = 0.005). CONCLUSIONS: Anti-BCMA CAR T-cell therapy is safe and effective for R/R multiple myeloma. For patients with high-risk factors, improvements to extend remission and more specific individualized therapies are needed.

9.
Asia Pac J Clin Nutr ; 30(3): 497-503, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34587709

RESUMO

BACKGROUND AND OBJECTIVES: Carotid intima-media thickness (IMT) is a risk predictor for myocardial infarction and stroke. Patients with type 2 diabetes mellitus are at higher risk for such conditions. The association of alcohol consumption with IMT is still controversial. METHODS AND STUDY DESIGN: We undertook a cross-sectional study of patients hospitalized in the Department of Endocrinology at Zhoushan Hospital from January 1st, 2013 to December 31st, 2015. Patients with a past medical history of cerebrovascular events, acute myocardial ischemia or unable to provide a detailed alcohol consumption history were excluded. Carotid IMT, together with blood biochemical examinations were collected. Data were analyzed using least significant difference t test, Tamhane's T2 test, Levene test, χ2-test and binary logistic regression model. RESULTS: 281 patients were enrolled in the study. The number of patients with elevated carotid IMT in moderate alcohol consumers was apparently less than alcohol non/heavy-consumers. In addition, the number of participants with elevated carotid IMT in liqueur consumers was higher than alcohol non-consumers and rice wine/beer consumers. Systolic blood pressure, C-reactive protein, glycosylated hemoglobin, low density lipoprotein cholesterol, triglyceride, gamma glutamyl transpeptidase, uric acid, cholesterol and creatinine levels were higher in elevated IMT patients, while high density lipoprotein cholesterol level was levels were significantly lower (p value<0.05). CONCLUSIONS: Moderate alcohol consumption has a protective effect on atherosclerosis in patients with type 2 diabetes mellitus, requiring consideration to dietary intake and physical activity, among other influences. Inflammation theory and lipid metabolism could be involved in such prophylaxis effects.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 2 , Consumo de Bebidas Alcoólicas , Espessura Intima-Media Carotídea , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Humanos
10.
Front Neurosci ; 15: 706786, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335176

RESUMO

The protective effects of repetitive transcranial magnetic stimulation (rTMS) on myelin integrity have been extensively studied, and growing evidence suggests that rTMS is beneficial in improving cognitive functions and promoting myelin repair. However, the association between cognitive improvement due to rTMS and changes in brain lipids remains elusive. In this study, we used the Y-maze and 3-chamber tests, as well as a mass spectrometry-based lipidomic approach in a CPZ-induced demyelination model in mice to assess the protective effects of rTMS on cuprizone (CPZ)-induced cognitive impairment and evaluate changes in lipid composition in the hippocampus, prefrontal cortex, and striatum. We found that CPZ induced cognitive impairment and remarkable changes in brain lipids, specifically in glycerophospholipids. Moreover, the changes in lipids within the prefrontal cortex were more extensive, compared to those observed in the hippocampus and striatum. Notably, rTMS ameliorated CPZ-induced cognitive impairment and partially normalized CPZ-induced lipid changes. Taken together, our data suggest that rTMS may reverse cognitive behavioral changes caused by CPZ-induced demyelination by modulating the brain lipidome, providing new insights into the therapeutic mechanism of rTMS.

11.
Int J Food Sci Nutr ; : 1-13, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34353205

RESUMO

The prevalence of obesity and its associated diseases is increasing. In the current study, 15 obese subjects took part in a 12-week multiphase dietetic protocol incorporating an improved ketogenic diet (MDP-i-KD) (KYLLKS 201806). We investigated the effects of the MDP-i-KD on the anthropometric parameters and the gut microbiota of obese subjects. Our results showed that the MDP-i-KD led to significant reductions in body mass index in obese subjects. The MDP-i-KD significantly decreased the relative abundance of the Lachnospiraceae_ND3007_group, the Eubacterium_hallii_group, and Pseudomonas and Blautia. In addition, gut microbiota co-occurrence networks in obese subjects were restructured to a more healthy condition after weight loss. These results show that the MDP-i-KD enhanced weight loss, which may be associated with dietary-induced changes in the gut microbiome. Our results emphasise the importance of determining the interaction between the host and microbial cells to comprehensively understand the mechanism by which diet affects host physiology and the microbiota.

12.
Front Pharmacol ; 12: 702152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366854

RESUMO

Background: Chimeric antigen receptor T cell (CAR-T) therapy is successful in improving treatment outcomes for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). However, toxicities associated with CAR-T therapy are being increasingly identified. Pancytopenia is one of the most common complications after CAR-T therapy, and platelet transfusions are an essential part of its supportive care. Study Design and Methods: This study aimed to assess the effectiveness of platelet transfusions for R/R ALL patients at our single center and identify associated risk factors. Overall, 44 R/R ALL patients were enrolled in this study, of whom 26 received CAR-T therapy and 18 received salvage chemotherapy. Result: Patients in the CAR-T group had a higher incidence of platelet transfusion refractoriness (PTR) (15/26, 57.7%) than those in the chemotherapy group (3/18, 16.7%) (p = 0.007). For patients receiving CAR-T therapy, multivariate analysis showed that the grade of cytokine release syndrome (CRS) was the only independent risk factor associated with PTR (p = 0.007). Moreover, higher peak serum IL-6 and IFN-γ levels suggested a higher risk of PTR (p = 0.024 and 0.009, respectively). Patients with PTR received more platelet infusion doses than those without PTR (p = 0.0426). Patients with PTR had more grade 3-4 bleeding events than those without PTR (21.4 vs. 0%, p = 0.230), and the cumulative incidence of grade 3-4 bleeding event was different (p = 0.023). Conclusion: We found for the first time that PTR is associated with the CRS grade. Improved knowledge on the mechanisms of PTR after CAR-T therapy is needed to design a rational therapeutic strategy that aims to improve the efficiency of transfusions.

13.
Front Oncol ; 11: 713577, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422666

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy has exhibited promising clinical outcomes in treating relapsed/refractory (R/R) B-cell hematologic malignancies. Current studies have shown a close correlation between baseline tumor burden and therapeutic response in CAR-T cell therapy. However, the roles of PET/CT metabolic parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), remain unclear in this setting. In this study, we retrospectively reviewed 41 R/R NHL patients. 18F-FDG PET/CT was used to measure the average standardized uptake value (SUVavg), MTV, and TLG of the lymphomatous lesions. These patients were divided into two groups according to the optimal cutoff values of respective PET/CT metabolic parameters. The multivariate analysis depicted that early post-therapy SUVavg (HR: 1.418, 95% CI: 1.029, 1.955; p = 0.033) and MTV (HR: 1.001, 95% CI: 1.000, 1.002; p = 0.041) were independent risk factors associated with OS and PFS, respectively. Patients with baseline SUVavg < 4.36 achieved a superior 1-year OS rate than the SUVavg ≥ 4.36 group (100.0% vs. 44.9%, p = 0.019). For the patients with lower values in early post-therapy SUVavg (<2.60) (51.1% vs. 0%, p < 0.001), MTV (<0.55 cm3) (53.6% vs. 0.0%, p = 0.001), and TLG (<1.54) (53.6% vs. 0.0%, p = 0.001), their 1-year PFS rates were higher than the compared groups. Moreover, patients with higher baseline tumor burdens were found to have significantly increased CRS incidence and cytokine levels. In conclusion, the PET/CT metabolic parameters are closely related to OS, PFS, and CRS in R/R NHL patients treated with CAR-T cells. This study may pave the way for building a comprehensive assessment system of tumor burden using 18F-FDG PET/CT, which can optimize therapeutic and supportive approaches in CAR-T cell therapy.

14.
Bioresour Technol ; 341: 125765, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34438287

RESUMO

Partial denitrification is an alternative process to provide stable nitrite for anammox. In this study, based on full-scale and lab-scale experiments, achieving and control of partial denitrification and the microbial mechanism were studied for 17 months in municipal wastewater treatment plant (MWWTP). Using glucose (GLC) as sole carbon source, partial denitrification was successfully achieved with nitrite accumulation percentage (NAP) higher than 90%; whereas, using sodium acetate (NaAc) as sole carbon source, nitrite accumulation was effectively controlled with economic and efficient carbon usage. Candidatus Competibacter and Thaurea were the dominant communities for partial denitrification. Denitrifying glycogen accumulating organisms (DGAOs), Thauera, denitrifying phosphorus accumulating organisms (DPAOs), GAOs, PAOs and denitrifiers coexisted in MWWTP, resulting in COD specific removal rate (CODSRR) of 883.10 ~ 1188.92mgN/gMLVSS/h during partial denitrification. Through adjustment of Anoxic-Oxic (A/O) operation to anoxic operation, the growth of GAOs and PAOs could be limited.


Assuntos
Desnitrificação , Purificação da Água , Reatores Biológicos , Nitrogênio , Fósforo , Esgotos , Eliminação de Resíduos Líquidos , Águas Residuárias
15.
Front Oncol ; 11: 702644, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277448

RESUMO

Although chimeric antigen receptor T (CAR-T) cell therapy has proven to be effective in treating relapsed or refractory B-cell hematological malignancies, severe hematological toxicities remain an intractable issue. This retrospective study assessed the characteristics and risk factors of new-onset severe cytopenia following CAR-T cell infusion in 76 patients with r/r acute lymphoblastic leukemia. The rates of new-onset severe cytopenia were high, including severe neutropenia (SN) (39/56, 70%), severe anemia (SA) (35/66, 53%), and severe thrombocytopenia (ST) (31/64, 48%). Comparatively, cohorts with higher cytokine release syndrome (CRS) grades had higher incidence of severe cytopenia with prolonged duration. Multivariable analyses showed that elevated maximum (max) lg D-dimer and delayed peak time of CRS are independent risk factors for SN recovery; increased max lg IL-10 and delayed CRS recovery are risk factors for SA; high max lg ferritin is a risk factor for ST; and longer period to CRS onset or CRS recovery and higher grade of CRS are risk factors for prolonged hematological toxicities. These observations led to the conclusion that profiles of CRS, including its duration, severity and serum markers are correlated to the incidence and recovery of new-onset severe cytopenia, prompting clinical intervention for post-CAR-T severe cytopenia.

16.
Front Oncol ; 11: 668099, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307138

RESUMO

Background: Extramedullary (EM) lesions are common in multiple myeloma (MM) and are often related to the poor prognosis of MM but are scarcely understood. Methods: In this retrospective study, the baseline characteristics of 357 newly diagnosed patients with extramedullary multiple myeloma (EMM) and their impact on the prognosis were analyzed. All patients received first-line treatment with bortezomib-based regimen. Results: The overall incidence rate of EM was 22.4%, and the detection rate of PET/CT was significantly higher than other imaging methods (P = 0.015). The cohorts consisted of 10 cases of extramedullary extraosseous (EME) and 70 cases of extramedullary-bone related (EMB), including 53 cases with single site involvement (one case with EME) and 27 cases with multiple sites (>1 site) involvement (nine cases with EME). EMM patients had high levels of hemoglobin (Hgb, ≥10 g/dl) and serum lactate dehydrogenase (LDH, >245u/L) and are inclined to early-stage revised international staging system (R-ISS). Compared to patients without EM, those with EMM had worse progression-free survival (PFS) (P = 0.014) and overall survival (OS) (P = 0.032). In addition, patients without EM and those with a single site of EMB had similar PFS and OS, while patients with multiple sites of EMB or EME and multiple sites of EMB with EME had poor PFS and OS. Multivariate analysis confirmed that multiple sites of EMB and/or EME were independent prognostic predictors affecting PFS and OS in newly diagnosed MM patients. Conclusions: This study suggested that among patients treated with bortezomib-based regimens, multiple sites of EMB and/or EME are independent poor prognostic factors for newly diagnosed MM patients, while a single site of EMB does not affect the survival of newly diagnosed MM patients. Thus, these findings could be used as a reference for the study of EMM patients in the new drug era, but prospective clinical studies are needed to provide evidence-based data for the diagnosis and treatment of EMM.

17.
Front Oncol ; 11: 665217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195075

RESUMO

Introduction: We analyzed different patient subgroups to determine optimal maintenance therapy in newly diagnosed multiple myeloma (NDMM) patients. Methods: A total of 226 NDMM patients in our center were included in the study. The characteristics, survival, and adverse reactions were compared among patients who received maintenance therapy or not, and patients who received proteasome inhibitors (PIs) or immunomodulators (IMiDs) maintenance. The survival of different maintenance durations of bortezomib-based regimens was also analyzed. Results: The maintenance therapy not only upgraded more patient responses (34.3 vs 13.3%, P = 0.006), but also significantly prolonged their progression-free survival (PFS) (median PFS: 41.1 vs 10.5 months, P < 0.001) and overall survival (OS) (median OS: not reached vs 38.6 months, P < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs 38.5 months, P = 0.034) and OS (median OS: not reached vs 78.5 months, P = 0.041) were both enhanced by PIs maintenance. Patients younger than 65 years who received PIs had a significantly prolonged OS (P = 0.032). Patients achieving only a partial response (PR) after induction and consolidation therapy had significantly longer PFS and OS after PIs maintenance compared to IMiDs (P = 0.007, 0.002). High-risk patients (ISS 2-3, DS 2-3, and RISS 2-3) given PIs maintenance benefit from a prolonged PFS (P = 0.002, 0.02, 0.06) and OS (P = 0.059, 0.047, 0.044, respectively) compared with IMiDs therapy. OS was significantly prolonged in patients who received ≥ 12 months of bortezomib-based maintenance therapy compared to those who were treated for < 12 months (P < 0.001), but no difference was observed in OS between patients who received 12 to 24 or ≥ 24 months of bortezomib-based maintenance therapy (P = 0.292). Conclusion: PIs maintenance was superior to IMiDs in overall PFS and OS. The beneficial effect was most evident in patients achieving PR after induction and consolidation therapy, and in high-risk patients. Moreover, younger patients also benefited from PIs maintenance with an increased OS. A bortezomib-based maintenance therapy duration of 12 to 24 months after induction and consolidation therapy produced satisfactory OS.

18.
Cancer Immunol Res ; 9(9): 1061-1070, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34290048

RESUMO

Chimeric antigen receptor (CAR) T-cell therapies that target either CD19 or CD22 alone have potent antilymphoma effects. However, antigen escape-mediated relapse often occurs. CAR T cells targeting both CD19 and CD22 may overcome this limitation. In this study, we developed bispecific CAR T cells simultaneously recognizing CD19- and CD22-expressing targets and assessed their safety and efficacy profiles in patients with relapsed/refractory aggressive B-cell lymphoma. Twenty-four patients were screened, and 16 were found eligible for the study. CAR T-cell-associated toxicities were recorded. Responses, overall survival (OS), and progression-free survival (PFS) were assessed. Of the 16 eligible patients, 14 (87.5%) achieved objective response and 10 (62.5%) achieved complete response (CR). The 2-year OS and PFS rates were 77.3% and 40.2%, respectively. Achieving CR (P = 0.046) and the number of prior chemotherapy lines (n = 2; P = 0.047) were independent prognostic factors associated with favorable PFS. The 2-year OS and PFS among patients who achieved CR were higher than among those who did not (P = 0.015 and P < 0.001, respectively). The 2-year PFS among patients who received two prior lines of chemotherapy was higher than that among patients who received more than two lines of chemotherapy (P = 0.049); OS did not differ between the groups. Severe grade 4 cytokine-release syndrome (CRS) was observed in 1 patient; 4 and 11 patients had grades 1 and 2 CRS, respectively. No patients developed neurotoxicity. CD19/CD22 dual-targeted CAR T cells may be a safe, potent antilymphoma cell-based targeted immunotherapy.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34281102

RESUMO

Exploring the flow intensity of virtual cultivated land is the key to improving the ecological compensation and food security policy. This study aimed to analyze the dynamic evolution, spatial convergence, and its affecting factors of the virtual cultivated land flow intensity. The spatial convergence model was used in this study. The results showed that, during 2000-2018, the growth rate of the surplus state of virtual cultivated land at the national level is less than that of the deficit state of virtual cultivated land in China. Moreover, the number of deficit provinces of virtual cultivated land flow intensity is increasing. The absolute ß-convergence characteristics of the virtual cultivated land flow intensity are significant at the national, northeast, central, and western regions. Additionally, the conditional ß-convergence exists at the national and four regional levels. Meanwhile, cultivated land resource endowment, population scale, regional economic development level, and agricultural mechanization level play an important role in the convergence process of inter-regional virtual cultivated land flow intensity. However, the influence degree of different control variables on different regional virtual cultivated land flow intensity is not consistent. Therefore, policymakers should pay attention to cultivated land resources' spatial transfer mechanism when making regional cultivated land ecological compensation policies to coordinate the interesting relationship between the deficit area and surplus area of virtual cultivated land. Therefore, it is necessary to take the virtual cultivated land flow intensity as the reference index and use the combination of market guidance and government control to stimulus the stakeholders to protect cultivated land by taking different measures.


Assuntos
Agricultura , Conservação dos Recursos Naturais , China , Fenômenos Físicos
20.
Cell Transplant ; 30: 9636897211025503, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34144648

RESUMO

Chimeric antigen receptor T cells (CAR-Ts) constitute a novel therapeutic strategy for relapsed/refractory B-cell malignancies. With the extensive application of CAR-T therapy in clinical settings, CAR-T-associated toxicities have become increasingly apparent. However, information regarding the associated infections is limited. We aimed to evaluate the incidence of infection during CAR-T therapy and identify the potential risk factors. Especially, we evaluated infections and the associated risk factors in 92 patients. The cohort included patients with acute lymphoblastic leukemia (n = 58) and non-Hodgkin lymphoma (n = 34). Fifteen cases of infection (predominantly bacterial) were observed within 28 days of CAR-T therapy, with an infection density of 0.5 infections for every 100 days-at-risk. Neutropenia before CAR-T therapy (P = .005) and prior infection (P = .046) were independent risk factors associated with infection within 28 days after CAR-T therapy; corticosteroid treatment during cytokine release syndrome (P = .013) was an independent risk factor during days 29-180 after CAR-T infusions. Moreover, the 2-year survival duration was significantly shorter in patients with infections than in those without (126 vs 409 days; P = .006). Our results suggested that effective anti-infection therapies may improve prognosis of patients who have a high infection risk. The risk of bacterial infections during the early stages of CAR-T therapy and the subsequent risk of viral infections thereafter should be considered to provide the appropriate treatment and improve patient prognosis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...