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1.
Int J Biol Macromol ; 262(Pt 2): 130143, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367775

RESUMO

A novel carrier comprised of ethanol- and alkali-modified cellulosic pomelo pith matrix coated with alginate was developed to improve viability while enabling gastrointestinal release of probiotics. Scanning electron microscopy imaging revealed the agricultural byproduct had a honeycomb-structured cellulose framework, enabling high loading capacity of the probiotic Lactobacillus plantarum up to 9 log CFU/g. Ethanol treatment opened up pores with an average diameter of 97 µm, while alkali treatment increased swelling and porosity, with an average pore size of 51 µm. The survival rate through the stomach was increased from 89.76 % to 91.08 % and 91.24 % after ethanol and alkali modification, respectively. The control group displayed minimal release in the first 4 h followed by a burst release. Both ethanol modification and alkali modification resulted in constant linear release over time. The release time was prolonged when decreasing the width of the pomelo peel rolls from 10 mm to 5 mm while keeping the volume of the peel constant. After 8 weeks of refrigerated storage, the cellulose-encapsulated probiotics retained viability above 7 log CFU/g. This study demonstrates the potential of the structurally intact, sustainably-sourced cellulosic pomelo pith for probiotic encapsulation and controlled delivery.


Assuntos
Alginatos , Probióticos , Celulose , Preparações de Ação Retardada , Álcalis , Etanol , Viabilidade Microbiana
2.
Sci Rep ; 14(1): 3036, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321043

RESUMO

Drawing upon self-determination theory, this study explores how listening music willingness (LMW) and music engagement (ME) impact musical development and achievement (MDA) via the mediating role of music aesthetic experience (MAE) and music listening behavior (MLB) among 299 university music students in Chinese higher educational institutions (HEIs). Employing structural equation modeling (SEM), the results reveal that LMW significantly influences MLB but not musical development and achievement. ME significantly affects both music aesthetic experience and MDA, with a significant correlation between MLB and MDA. Besides, the relationship between MAE and MDA is positively significant. Mediation analysis reveals that music listening behavior fully mediates the LMW-MDA relationship, while the relationship between ME and MDA is partially mediated by musical aesthetic experience. These findings offer insights for crafting music educational strategies emphasizing positive listening behavior, active engagement, and enriched aesthetic experiences to enhance effectiveness in HEIs. For policymakers particularly in China, understanding the pivotal role of MLB as a mediator between willingness and achievement suggests interventions targeting listening habits can positively influence overall MDA. Furthermore, recognizing the partial mediation by aesthetic experience in the relationship between engagement and MDA suggests programs enhancing musical aesthetic experiences could amplify the impact of music education initiatives.


Assuntos
Música , Humanos , Universidades , Instituições Acadêmicas , Estudantes , China
3.
EClinicalMedicine ; 68: 102431, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38318126

RESUMO

Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).

5.
Spine J ; 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37918569

RESUMO

BACKGROUND CONTEXT: Enhanced recovery after surgery (ERAS) has proven beneficial for patients undergoing orthopedic surgery. However, the application of ERAS in the context of metastatic epidural spinal cord compression (MESCC) remains undefined. PURPOSE: This study aims to establish a medical pathway rooted in the ERAS concept, with the ultimate goal of scrutinizing its efficacy in enhancing postoperative outcomes among patients suffering from MESCC. STUDY DESIGN/SETTING: An observational cohort study. PATIENT SAMPLE: A total of 304 patients with MESCC who underwent surgery were collected between January 2016 and January 2023 at two large tertiary hospitals. OUTCOME MEASURES: Surgery-related variables, patient quality of life, and pain outcomes. Surgery-related variables in the study included surgery time, surgery site, intraoperative blood loss, and complication. METHODS: From January 2020 onwards, ERAS therapies were implemented for MESCC patients in both institutions. Thus, the ERAS cohort included 138 patients with MESCC who underwent surgery from January 2020 to January 2023, whereas the traditional cohort consisted of 166 patients with MESCC who underwent surgery from January 2016 to December 2019. Clinical baseline characteristics, surgery-related features, and surgical outcomes were collected. Patient quality of life was evaluated using the Functional Assessment of Cancer Therapy-General Scale (FACT-G), and pain outcomes were assessed using the Visual Analogue Scale (VAS). RESULTS: Comparison of baseline characteristics revealed that the two cohorts were similar (all p>.050), indicating comparable distribution of clinical characteristics. In terms of surgical outcomes, patients in the ERAS cohort exhibited lower intraoperative blood loss (p<.001), shorter postoperative hospital stays (p<.001), lower perioperative complication rates (p=.020), as well as significantly shorter time to ambulation (P<0.001), resumption of regular diet (p<.001), removal of urinary catheter (p<.001), initiation of radiation therapy (p<.001), and initiation of systemic internal therapy (p<.001) compared with patients in the traditional cohort. Regarding pain outcomes and quality of life, patients undergoing the ERAS program demonstrated significantly lower VAS scores (p<.010) and higher scores for physical (p<.001), social (p<.001), emotional (p<.001), and functional (p<.001) well-being compared with patients in the traditional cohort. CONCLUSIONS: The ERAS program, renowned for its ability to expedite postoperative recuperation, emerges as a promising approach to ameliorate the recovery process in MESCC patients. Not only does it exhibit potential in enhancing pain management outcomes, but it also holds the promise of elevating the overall quality of life for these individuals. Future investigations should delve deeper into the intricate components of the ERAS program, aiming to unravel the precise mechanisms that underlie its remarkable impact on patient outcomes.

6.
Ann Hematol ; 102(11): 3185-3193, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37700194

RESUMO

The aim of this study is to evaluate the survival benefit of consolidative autologous hematopoietic stem cell transplantation (ASCT) in patients with peripheral T-cell lymphomas (PTCL). In this retrospective study, the ASCT group underwent consolidative ASCT after first-line therapy at 14 transplantation centers in China between January 2001 and December 2019. Data were collected over the same time frame for the non-ASCT group from the database of lymphoma patient records at Peking University Cancer Hospital & Institute. A total of 120 and 317 patients were enrolled in the ASCT and non-ASCT groups, respectively, and their median ages were 43 years and 51 years, respectively. In the ASCT group, 101 patients had achieved complete remission (CR) and 19 patients had achieved partial remission at the time of ASCT. The median follow-up time was 40.2 months and 68 months, and the 3-year overall survival (OS) rate was 80.6% and 48.9% (p < 0.001) for the ASCT and non-ASCT groups, respectively. The beneficial effect of ASCT for OS remained even after propensity score-matched (PSM) analysis (81.6% vs 68.3%, p = 0.001). Among the 203 patients who were aged ≤ 65 years and achieved CR, ASCT conferred a significant survival benefit (3-year progression-free survival [PFS]: 67.4% vs 47.0%, p = 0.004; 3-year OS: 84.0% vs 74.1%, p = 0.010), and this was also maintained after PSM analysis (3-year PFS: 66.6% vs 48.4%, p = 0.042; 3-year OS: 84.8% vs 70.5%, p = 0.011). Consolidative ASCT improved the survival outcome of PTCL patients, even those who achieved CR after first-line therapy.

7.
Am J Hematol ; 98(11): 1742-1750, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37647123

RESUMO

Marginal zone lymphoma (MZL) is an indolent type of non-Hodgkin lymphoma that develops through pathological B cell receptor signaling. Orelabrutinib, a new-generation oral small molecule Bruton's tyrosine kinase inhibitor, was evaluated in relapsed/refractory (r/r) MZL patients. Previously treated r/r MZL patients received orelabrutinib 150 mg once daily in a phase 2, multicenter, single-arm study conducted in China. The primary endpoint was overall response rate (ORR) assessed by an Independent Review Committee (IRC) based on the Lugano 2014 classification. Other efficacy, safety, and pharmacokinetic profiles were evaluated as secondary outcome measures. A total of 111 patients were enrolled, of which 90 patients had MZL confirmed by central pathology review, who were mainly with extra-nodal MZL of mucosa-associated lymphoid tissue (MALT, 46.7%) and nodal MZL (35.6%). The majority had late-stage disease, with stage IV accounting for 75.6%. After a median follow-up duration of 24.3 months, the IRC-assessed ORR was 58.9% (95% confidence interval [CI], 48.0-69.2), with rates of complete response and partial response being 11.1% and 47.8%, respectively. The IRC-assessed median duration of response was 34.3 months, and the IRC-assessed median progression-free survival (PFS) was not reached with a 12-month PFS rate of 82.8% (95% CI, 72.6-89.5). The rate of overall survival at 12 months was 91.0% (95% CI, 82.8-95.4). Common all-grade treatment-related adverse events (TRAEs) included anemia (27.9%), neutrophil count decrease (23.4%), white blood cell count decrease (18.0%), platelet count decrease (17.1%), blood present in urine (16.2%), rash (14.4%), and upper respiratory tract infection (10.8%). Thirty-four patients (30.6%) experienced grade 3 or higher TRAEs. Serious TRAEs occurred in 18 patients (16.2%), of which pneumonia (5.4%) was the most common. Seven patients (6.3%) discontinued orelabrutinib due to TRAEs. Orelabrutinib demonstrated high response rates with durable disease remission and was well tolerated in Chinese patients with r/r MZL.

8.
Front Psychol ; 14: 1121180, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37519375

RESUMO

Based on social cognitive theory (SCT), the purpose of this study is to examine the role of music attitude and its essential precursors in stimulating the psychological wellbeing of immigrants in isolation (quarantine) during the COVID pandemic. This study employed quantitative methodology; an online survey was administered to collect sufficient data from 300 immigrants who traveled to China during the pandemic. Data were collected from five centralized quarantine centers situated in different cities in China. Additionally, the valid data set was analyzed using structural equation modeling (SEM) via AMOS 24 and SPSS 24. The results indicate that potential predictors such as cognitive - music experience (MEX), environmental - social media peer influence (SPI), and cultural factors such as native music (NM) have a direct, significant, and positive effect on music attitude (MA), which further influences immigrants' psychological wellbeing (PW) during their quarantine period. Moreover, in the presence of the mediator (MA), the mediating relationships between MEX and PW, and NM and PW, are positive, significant, and regarded as partial mediation. However, the moderated mediation effects of music type (MT) on MEX-MA-PW and NM-MA-PW were found to be statistically not significant and unsupported. This study contributes to the literature on the effectiveness of individuals' music attitude and its associated outcomes, focusing on mental health care in lonely situations such as quarantine during the COVID pandemic. More importantly, this study has raised awareness about music, music attitude, and their beneficial outcomes, such as mental calmness and peacefulness for the general public, particularly during social distancing, isolation, and quarantine in the COVID pandemic situation.

9.
Lancet Reg Health West Pac ; 34: 100720, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37283978

RESUMO

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

10.
Cancer Med ; 12(12): 13204-13216, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37148540

RESUMO

BACKGROUND: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. METHODS: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. RESULTS: The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. CONCLUSIONS: First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.


Assuntos
Linfoma de Célula do Manto , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/epidemiologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina , Intervalo Livre de Progressão , Resultado do Tratamento
11.
Am J Cancer Res ; 13(4): 1571-1581, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168343

RESUMO

Renal impairment (RI) is a very common complication of multiple myeloma (MM) with a negative impact on survival. Herein we retrospectively analyzed 334 MM patients with renal impairment at diagnosis from three hospitals in China. All 334 patients were divided into three groups, including dialysis dependence (n=43), dialysis independence (n=42), and without dialysis (n=249). Compared with dialysis independence and without dialysis groups, dialysis dependence group had the lowest overall hematologic response (48.8% vs. 97.6% vs. 77.1%, P<0.001) and overall renal response (0.0% vs. 97.6% vs. 72.7%, P<0.001), as well as the highest early mortality within 24 months (50.0% vs. 24.4% vs. 26.3%, P=0.006). Dialysis dependence group had similar progression-free survival (24 vs. 26 vs. 27 months, P=0.231) and significantly shorter overall survival (25 vs. 69 vs. 45 months, P=0.001). Dialysis dependence was independently associated with high mortality within 24 months and shorter overall survival. In conclusion, MM patients with dialysis dependence still tend to suffer a dismal disease course, including a high probability to suffer early mortality, worse hematological and renal response, as well as shorter survival. Dialysis independence could be very promising for survival improvement.

12.
Eur J Haematol ; 110(6): 680-687, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36825748

RESUMO

OBJECTIVES: The advanced extra-nodal NK/T-cell lymphoma (ENKTL) is highly aggressive and lacks effective treatment with a poor prognosis. This study aimed to investigate the effectiveness and safety of autologous hematopoietic stem cell transplantation (ASCT) in CR1. METHODS: Forty of 121 patients with advanced ENKTL from four Chinese hospitals between January 2006 to December 2021 who achieved first complete remission (CR1) and received at least 4 cycles chemotherapy, were enrolled for analysis. Twenty patients received ASCT as up-front consolidation therapy (Group A), and 20 patients only received chemotherapy (Group B). Clinical features, treatment and follow-up information were collected. RESULTS: With a median follow-up of 27 months (range, 4-188 months), the 2-year overall survival (OS) in Group A, 61% (95% CI 37%-85%), was better than that in Group B, 26% (95% CI 2%-50%), p = .018. The 2-year progression-free survival (PFS) was 56% (95% CI 32%-80%) in Group A, 26% (95% CI 2%-50%) in Group B, p = .026. III-IV grade hematological toxicity was the most common adverse event. No treatment-related deaths were observed in both groups. CONCLUSION: Up-front ASCT could improve survival of advanced ENKTL patients in first complete remission, but need be confirmed by a prospective clinical trial.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Extranodal de Células T-NK , Linfoma de Células T Periférico , Células T Matadoras Naturais , Humanos , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Prognóstico , Linfoma de Células T Periférico/etiologia
13.
Ann Transplant ; 28: e938467, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36593744

RESUMO

BACKGROUND Myeloablative chemotherapy supported by autologous stem cell transplantation (ASCT) is an option for primary central nervous system lymphoma (PCNSL) in both the relapse setting and as postremission consolidation, but the level of evidence in this field is still low. MATERIAL AND METHODS We retrospectively analyzed 47 HIV-negative PCNSL patients from 2010 to 2021. To assess the outcomes in patients undergoing ASCT. RESULTS Of the 47 patients, the median age was 51 (range, 21-77) years, and 28 (59.6%) were male. After induction, 33 (70.2%) patients achieved complete remission, and 6 (12.8%) patients achieved partial remission. At a median follow-up of 21.4 months (95% CI 8.86-33.95), the median progression-free survival (PFS) was 23.3 months (95% CI 14.87-31.73), and the 4-year PFS rate was 14.6%. The median overall survival (OS) time was 62.4 months (95% CI 41.93-82.87), and the 4-year OS rate was 71.5%. Among 20 patients who received ASCT (10 consolidation, 10 salvage), the 4-year PFS and 4-year OS rates were 57.3% and 71.2%, respectively. In the multivariate analysis, ASCT therapy (hazard ratio [HR] 0.16, P=0.016) and early remission (HR 0.12, p=0.003) were found to be independent prognostic factors for a longer PFS. Two treatment-related deaths occurred in patients with multiple relapses before ASCT. Pancytopenia and diarrhea were the most common adverse events. CONCLUSIONS ASCT offers potential long-term PFS with good tolerability for patients with PCNSL. Our retrospective cohort adds to the currently available literature and identifies disease status after induction as a significant factor affecting survival.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Transplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva , Linfoma/cirurgia , Sistema Nervoso Central , Transplante de Células-Tronco
14.
Cancer Lett ; 553: 215996, 2023 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-36343787

RESUMO

V-set and immunoglobulin domain containing 4 (VSIG4), a type I transmembrane receptor exclusively expressed in a subset of tissue-resident macrophages, plays a pivotal role in clearing C3-opsonized pathogens and their byproducts from the circulation. VSIG4 maintains immune homeostasis by suppressing the activation of complement pathways or T cells and inducing regulatory T-cell differentiation, thereby inhibiting the development of immune-mediated inflammatory diseases but enhancing cancer progression. Consequently, VSIG4 exhibits a potential therapeutic effect for immune-mediated inflammatory diseases, but also is regarded as a novel target of immune checkpoint inhibition in cancer therapy. Recently, soluble VSIG4, the extracellular domain of VSIG4, shed from the surface of macrophages, has been found to be a biomarker to define macrophage activation-related diseases. This review mainly summarizes recent new findings of VSIG4 in macrophage phagocytosis and immune homeostasis, and discusses its potential diagnostic and therapeutic usage in infection, inflammation, and cancer.


Assuntos
Neoplasias , Receptores de Complemento , Camundongos , Animais , Humanos , Receptores de Complemento/metabolismo , Camundongos Knockout , Camundongos Endogâmicos C57BL , Neoplasias/terapia , Biologia
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(5): 1590-1596, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36208271

RESUMO

OBJECTIVE: To explore the transcriptional gene expression profile up-regulated in human macrophages stimulated by interferon-γ (IFN-γ) and the underlying intracellular signaling mechanisms. METHODS: RNA-seq was used to sequence and compare the differential gene expression profiles of human macrophage cell line U937 before and after IFN-γ stimulation, and the significantly up-regulated genes were screened out, which were verified by fluorescence-based real-time quantitative polymerase chain reaction (qPCR) in U937 and THP1 cell lines, respectively. JAK/STAT, MAPK/ERK and PI3K/AKT pathway inhibitors were added to simultaneously to the cultured U937 cells upon IFN-γ priming to detect their effects on the expressions of the up-regulated genes to explore the key regulatory mechanisms. RESULTS: RNA-seq and qPCR results showed that, the well-recognized chemokines CXCL9, CXCL10 and CXCL11, the APOL family including APOL1, APOL2, APOL3, APOL4, APOL6 and GBP family GBP1, GBP2, GBP3, GBP4 and GBP5 as well were significantly up-regulated in IFN-γ-stimulated U937 cells. JAK/STAT3 pathway inhibitor inhibited the upregulation of APOL1, APOL4, GBP1, GBP4 and GBP5 genes induced by IFN-γ, while MAPK/ERK pathway inhibitor inhibited the upregulation of CXCL10 gene. PI3K/AKT pathway inhibitor inhibited the upregulation of APOL1,APOL4, APOL6, GBP1 and GBP5 genes induced by IFN-γ, all three signal pathway inhibitors could inhibit the upregulation of CXCL9 gene, and none of them could inhibit the upregulation of APOL3 gene. CONCLUSION: Upon IFN-γ stimulation, some family molecules of APOL and GBP in macrophages are significantly up-regulated, and PI3K/AKT, JAK/STAT3 and MAPK/ERK pathways have positive regulation on their expressions, respectively.


Assuntos
Apolipoproteína L1 , Interferon gama , Apolipoproteína L1/farmacologia , Humanos , Interferon gama/farmacologia , Macrófagos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
17.
Ann Hematol ; 101(2): 397-408, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34735613

RESUMO

Persistent thrombocytopenia (PT) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of bleeding and poor survival. The exact pathogenesis underlying PT remains unclear, and its management is difficult. Here we conducted a retrospective study to evaluate the efficacy and safety of eltrombopag (EPAG) in 34 patients with PT after allo-HSCT. Seven patients suffered from prolonged isolated thrombocytopenia (PIT), and 27 had secondary failure of platelet recovery (SFPR). For most patients, the initial dose was 25 mg or 50 mg daily, then adjusted to the maximum dose of 50-100 mg per day according to the response of platelet recovery and toleration of patients. The cumulative incidence (CI) of platelet recovery to at least 20 × 109/L and 50 × 109/L without transfusion support for at least 7 days was 72.1% and 60.7%, respectively. Nineteen (86.4%) of 22 responders were able to taper off the medication; furthermore, the platelet counts remained stable 1 month after withdrawal of EPAG. Although two patients discontinued EPAG during treatment due to headache and nausea, no patients developed grade 3 or 4 toxicities. Hypoplasia of bone marrow and decreased megakaryocytes (MKs) were found to be risk factors for overall response (OR) and complete response (CR) in multivariate analysis, respectively. Overall, our results indicated that EPAG can be used in the treatment of PT and that continuous exposure to EPAG may not be necessary.


Assuntos
Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico , Pirazóis/uso terapêutico , Trombocitopenia/terapia , Adolescente , Adulto , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Feminino , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do Tratamento , Adulto Jovem
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1181-1186, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362500

RESUMO

OBJECTIVE: To investigate the prognostic value of metabolic parameters of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 58 patients with DLBCL who were examined by 18F-FDG PET/CT before treatment and confirmed by pathology were analyzed retrospectively. The relationships between maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and clinical factors were analyzed. Kaplan Meier method, Log-rank test and multivariate Cox regression were used to analyze the relationships between metabolic SUVmax, MTV, TLG and times of total overall survival (OS) and progression-free survival (PFS). RESULTS: The SUVmax, MTV and TLG of 58 DLBCL patients were 21.45 (10.26-42.38), 27.30 (14.20-133.25) cm3 and 322.85 (47.35-1438.20), respectively. Univariate analysis showed that large mass, Ann Arbor stage, international prognostic index, MTV and TLG were the factors influencing OS and PFS in DLBCL patients (P<0.05), while lactate dehydrogenase and SUVmax were the factors influencing PFS only (P<0.05). Multivariate analysis showed that MTV (HR=2.974, 95%CI: 1.803-7.225)/(HR=3.925, 95%CI: 1.973-8.246) and TLG (HR=2.583, 95%CI: 1.192-5.316)/(HR=2.874, 95%CI: 1.538-6.483) were independent risk factors for OS and PFS in DLBCL patients (P<0.05), and international prognostic index (HR=2.490, 95%CI: 1.150-4.962) was independent risk factor for OS in DLBCL patients (P<0.05). CONCLUSION: MTV and TLG are independent risk factors for OS and PFS in patients with DLBCL, which may be valuable for prognosis of patients with DLBCL.


Assuntos
Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos
19.
Chin Med J (Engl) ; 134(13): 1584-1592, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34133361

RESUMO

BACKGROUND: There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China. METHODS: From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups. RESULTS: Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300). CONCLUSIONS: Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , China , Humanos , Linfoma de Células T Periférico/terapia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
20.
Chin Med J (Engl) ; 134(12): 1431-1440, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34091525

RESUMO

BACKGROUND: The impacts of previous cardio-cerebrovascular disease (pre-CCVD) on the outcomes of hematopoietic cell transplantation (HCT) are not well described. Patients with pre-CCVD may often be poor candidates for HCT. This study aimed to investigate the impact of pre-CCVD on transplant outcomes. METHODS: A retrospective study was conducted between patients with and without pre-CCVD who consecutively received allogeneic or autologous HCT between November 2013 and January 2020 with a matching of age and disease status. The cardiovascular complications and HCT outcomes of the two groups were evaluated and compared. The primary endpoints were post-transplant cardio-cerebrovascular disease (post-CCVD) and non-relapse mortality (NRM). We used a multivariable Cox proportional hazard model and the Fine-Gray competing risk regressions for analyses to estimate the hazard ratios (HRs). RESULTS: The outcomes of 23 HCT recipients with pre-CCVD were compared with those of 107 patients in the control group. No significant differences were noted in terms of engraftment, overall survival (OS) (67.00% vs. 67.90%, P = 0.983), or relapse (29.78% vs. 28.26%, P = 0.561) between the pre-CCVD group and the control group. The cumulative incidences of 2-year NRM were similar between patients with pre-CCVD and the controls (14.68% vs. 17.08%, P = 0.670). However, pre-CCVD was associated with an increased incidence of post-CCVD (HR: 12.50, 95% confidence interval [CI]: 3.88-40.30, P < 0.001), which was an independent risk factor for increased NRM (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001) and inferior OS (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001). CONCLUSIONS: These findings suggest that the existence of pre-CCVD before transplantation might not result in increased mortality directly but superpose the toxicity of the transplantation procedure, leading to a risk of post-CCVD. Post-CCVD was a powerful predictor for high NRM and inferior OS. Further risk stratification of pre-CCVD is needed to reduce NRM in various transplantation settings.


Assuntos
Transtornos Cerebrovasculares , Transplante de Células-Tronco Hematopoéticas , Transtornos Cerebrovasculares/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Autólogo
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