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OBJECTIVE: To investigate the effect of flow cytometric minimal residual disease (MRD) detection at different time points during AML chemotherapy on prognosis. METHODS: 130 adult primary AML patients diagnosed and standardized with chemotherapy from March 2018 to March 2022 were retrospectively analyzed, MRD was detected by flow cytometry, Kaplan-Meier curves was used for survival analysis and log-rank test was used for variance analysis, and univariate and multifactor influencing patient survival with COX proportional risk regression model analysis. Cumulative incidence rate (CIR) analysis with competing risk model and variance analysis using Fine-Gray. RESULTS: There were 81 CR1, 26 CR2, 14 PR, and 9 NR patients in 130 patients. OS of the CR1 group was higher than that in the CR2, PR,and NR groups. OS of the CR2 group was higher than that in the PR group, but there was no statistically difference compared to the NR group. There was no statistically difference in OS between the PR and NR groups. 107 patients in CR1 and CR2 were grouped according to MRD detected by flow cytometry, and after the first induction chemotherapy, for patients in the MRD- and MRD+ groups, the 4-year expected RFS rates were 65.3% and 27.9% respectively, the 4-year expected OS rates were 58.7% and 41.4% respectively, and the 4-year expected CIR were 34.7% and 69.7% respectively, with statistically significant differences between 2 groups (χ2=6.639, P =0.010; χ2=6.131, P =0.013 and χ2=6.637ï¼ P =0.010). After the second chemotherapy, for patients in the MRD- and MRD+ groups, the 4-year expected RFS rates were 50.8% and 37.9% respectively, the 4-year expected OS rates were 49.2% and 44.5% respectively, and the 4-year expected CIR were 49.2% and 59.5% respectively, with no statistically significant differences between 2 groups (χ2=1.475, P =0.225; χ2=2.432, P =0.119 and χ2=1.416ï¼ P =0.234). During consolidation therapy, for patients in the MRD - and MRD+ groups, the 4-year expected RFS rates were 51.9% and 29.6% respectively, the 4-year expected OS rates were 67.5% and 24.6% respectively, and the 4-year expected CIR were 48.1% and 70.4% respectively, with statistically significant differences between 2 groups (χ2=20.982, P < 0.001; χ2=17.794, P < 0.001 and χ2=19.879ï¼ P < 0.001). For patients with MRD- at all three time points and positive at either time point, the 4-year expected RFS rates were 69.9% and 33.3% respectively, the 4-year expected OS rates were 59.1% and 44.7% respectively, and the 4-year expected CIR were 30.1% and 65.1% respectively, with statistically significant differences between 2 groups (χ2=7.367, P =0.007; χ2=6.042, P =0.014 and χ2=7.662ï¼ P =0.006). Univariate analysis showed that karyotype at high risk of chromosome was an unfavorable factor affecting patients' RFS and OS, while 2 cycles of induction chemotherapy achieved CR, MRD- after the first induction chemotherapy and MRD- after the second induction chemotherapy was a protective factor affecting patients' RFS and OS. MRD- during consolidation therapy and MRD- at all three time points were all protective factors affecting patients' RFS, OS and CIR. Multivariate analysis showed that induction chemotherapy for 2 cycles achieved CR was a protective factor affecting patients' RFS and CIR, and MRD- during consolidation therapy was a protective factor affecting patients' RFS, OS and CIR. CONCLUSION: Early achievement of CR and MRD- in adult AML patients, especially MRD- during consolidation therapy, is a marker of good prognosis, and flow cytometry is the most commonly used method for MRD detection in AML patients.
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Citometría de Flujo , Leucemia Mieloide Aguda , Neoplasia Residual , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Femenino , Masculino , Modelos de Riesgos ProporcionalesRESUMEN
Trace NO2 detection is essential for the production and life, where the sensing strategy is appropriate for rapid detection but lacks molecular specificity. This investigation proposes a sensing mechanism dominated by surface-scattering to achieve the molecularly-specific detection. Two-dimensional Bi2O2Se is firstly fabricated into a Schottky-junction-based gas-sensor. Applied with an alternating excitation, the sensor simultaneously outputs multiple response signals (i.e., resistance, reactance, and the impedance angle). Their response times are shorter than 200 s at room temperature. In NO2 sensing, these responses present the detection limit in ppt range and the sensitivity is up to 16.8 %·ppb-1. This NO2 sensitivity presents orders of magnitude higher than those of the common gases within the exhaled breath. The impedance angle is involved in the principle component analysis together with the other two sensing signals. Twelve kinds of typical gases containing NO2 are acquired with molecular characteristics. The change in dipole moment of the target molecule adsorbed is demonstrated to correlate with the impedance angle via surface scattering. The proposed mechanism is confirmed to output ultra-sensitive sensing responses with the molecular characteristic.
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High-quality conjugated microporous polymer (CMP) films with orientation and controlled structure are extremely desired for applications. Here, we report the effective construction of CMP 3D composite films (pZn/PTPCz) with a controlled porosity structure and preferred orientation using the template-assisted electropolymerization (EP) approach for the first time. The structure of pZn/PTPCz composite thin films and nitrophenol sensing performance were thoroughly studied. When compared to the control CMP film made on flat indium tin oxide (ITO) substrates, the as-prepared pZn/PTPCz composite films showed significantly enhanced fluorescent intensity and much better sensing performance for the model explosive. This was attributed to the metal-enhanced fluorescence (MEF) of porous nanostructured zinc (pZn) and the additional macroporosity of the pZn/PTPCz composite films. This work provides a feasible approach for creating oriented 3D CMP-based thin films for advanced applications.
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This paper presents a one-step photochemical method for the preparation of CdS/Poly(MMA-co-MAA) composite photocatalyst, based on the concept of simultaneous photocatalytic polymerization of organic monomers during UV-light induced formation of CdS. The preparation is carried out in an aqueous solution of Na2S2O3, CdSO4, methyl methacrylate (MMA) and methacrylic acid (MAA), under a UV lamp. The continuously formed CdS particles with photocatalytic activity act the role of initiator to directly initiate the copolymerization of MMA and MAA, resulting in the inâ situ formation of the composite and full contact of the CdS particles with the oxygen-containing groups in the polymer. Taking the photocatalytic degradation of methylene blue as a case study, the composite exhibited significantly higher activity under simulated solar light compared to the pure CdS. By analysis on various data, the enhanced photocatalytic activity is attributed to the enhanced visible light absorption, and especially the high electron-hole separation efficiency caused by the electrostatic interaction between photogenerated holes and carbonyl oxygen atoms with negatively charged features. Furthermore, the composite displays excellent sunlight activity and recyclability, suggesting its potential for practical applications. Such a one-step construction strategy relying only on photo-energy is green, low-cost and promising in obtaining high-performance semiconductor/polymer composite photocatalysts.
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High-temperature environments pose significant risks to human health and safety. The body's natural ability to regulate temperature becomes overwhelmed under extreme heat, leading to heat stroke, dehydration, and even death. Therefore, the development of effective personal thermal-moisture management systems is crucial for maintaining human well-being. In recent years, significant advancements have been witnessed in the field of textile-based cooling systems, which utilize innovative materials and strategies to achieve effective cooling under different environments. This review aims to provide an overview of the current progress in textile-based personal cooling systems, mainly focusing on the classification, mechanisms, and fabrication techniques. Furthermore, the challenges and potential application scenarios are highlighted, providing valuable insights for further advancements and the eventual industrialization of personal cooling textiles.
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Visual interaction is a promising strategy for the externalized expression and transmission of information, having wide application prospects in wearable luminous textiles. Achieving an autonomous luminous display and dynamic light response to environmental stimuli is attractive but attracts little attention. Herein, we propose a liquid responsive structure based on alternating-current electroluminescent fibers and demonstrate conductive-liquid-bridging electroluminescent fabrics with high integration and personalized patterns. Impressively, our electroluminescent fibers and textiles could afford a sensitive response and high robustness to water, glycerol, ethanol, and sodium chloride solution. The final electroluminescent textiles show an excellent luminescence performance of 149.08 cd m-2. On the proof of concept, a rain-sensing umbrella, luminous sportswear, and liquid response glove are fabricated to demonstrate water detection, visual interaction, and environmental warning. The textile-type visualizing-responding strategy proposed in this work may open up new avenues for the application of ACEL devices in the field of visual interaction.
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Endocannabinoid system (ECS), which composed of its ligands and receptors, widely distributes in peripheral tissues and nerve system. Through complex regulating mechanisms, ECS exerts a variety of biological functions including analgesia. Its utility in analgesic regulation has attracted extensive attention, and the related achievements have also been transformed into clinical practice. With the deepened understanding of the essence of pain, as well as the advances in research techniques, quantity of research evidences showed that ECS could be regulated by acupuncture treatment and exerted analgesic effect in inflammatory pain, neuropathic pain and other related diseases, and the mechanism had also been revealed gradually. By reviewing literatures related to acupuncture analgesia and ECS, we summarized the effect and mechanism of acupuncture analgesia involved with regulation of ECS, pointed out cannabinoid (CB) 1 receptor and CB2 receptor exerted analgesic effect in central and peripheral neural system through mechanisms of inhibiting neural activation and anti-inflammation, respectively. Therefore, we hope to provide reference and inspiration for relevant research and clinical practice in the future.
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Terapia por Acupuntura , Analgesia , Neuralgia , Humanos , Endocannabinoides , Manejo del DolorRESUMEN
AIM: We aimed to study the influence of sevoflurane on the nucleotide-binding domain and Leucine-rich repeat protein 3 (NLRP3) pathways in rats with cerebral ischemia/reperfusion (I/R) injury. METHODS: Sixty Sprague-Dawley rats were equally divided into five groups randomly: sham-operated, cerebral I/R, sevoflurane (Sevo), NLRP3 inhibitor-treated (MCC950), and sevoflurane and NLRP3 inducer-treated groups. Rats' neurological functions were assessed using Longa scoring after 24 h of reperfusion, after which they were sacrificed, and cerebral infarction area was determined by triphenyl tetrazolium chloride staining. Pathological changes in damaged portions were assessed using hematoxylin-eosin and Nissl staining, and cell apoptosis was detected by terminal-deoxynucleotidyl transferase-mediated nick end labeling staining. Interleukin 1 beta (IL-1ß), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18), malondialdehyde (MDA), and superoxide dismutase (SOD) levels in brain tissues were determined using enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) levels were analyzed using a ROS assay kit. Protein levels of NLRP3, caspase-1, and IL-1ß were determined by western blot. RESULTS: Neurological function scores, cerebral infarction areas, and neuronal apoptosis index were decreased in the Sevo and MCC950 groups than in the I/R group. IL-1ß, TNF-α, IL-6, IL-18, NLRP3, caspase-1, and IL-1ß levels decreased in the Sevo and MCC950 groups (p < 0.05). ROS and MDA levels increased, but SOD levels increased in the Sevo and MCC950 groups than in the I/R group. NLPR3-inducer nigericin eliminated the protective effects of sevoflurane on cerebral I/R injury in rats. CONCLUSION: Sevoflurane could alleviate cerebral I/R-induced brain damage by inhibiting the ROS-NLRP3 pathway.
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Isquemia Encefálica , Daño por Reperfusión , Ratas , Animales , Sevoflurano/farmacología , Ratas Sprague-Dawley , Interleucina-18 , Especies Reactivas de Oxígeno/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-6 , Factor de Necrosis Tumoral alfa/metabolismo , Enfermedades Neuroinflamatorias , Isquemia Encefálica/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Caspasa 1/metabolismo , Infarto Cerebral/tratamiento farmacológico , Reperfusión , Superóxido DismutasaRESUMEN
Fibers, originating from nature and mastered by human, have woven their way throughout the entire history of human civilization. Recent developments in semiconducting polymer materials have further endowed fibers and textiles with various electronic functions, which are attractive in applications such as information interfacing, personalized medicine, and clean energy. Owing to their ability to be easily integrated into daily life, soft fiber electronics based on semiconducting polymers have gained popularity recently for wearable and implantable applications. Herein, we present a review of the previous and current progress in semiconducting polymer-based fiber electronics, particularly focusing on smart-wearable and implantable areas. First, we provide a brief overview of semiconducting polymers from the viewpoint of materials based on the basic concepts and functionality requirements of different devices. Then we analyze the existing applications and associated devices such as information interfaces, healthcare and medicine, and energy conversion and storage. The working principle and performance of semiconducting polymer-based fiber devices are summarized. Furthermore, we focus on the fabrication techniques of fiber devices. Based on the continuous fabrication of one-dimensional fiber and yarn, we introduce two- and three-dimensional fabric fabricating methods. Finally, we review challenges and relevant perspectives and potential solutions to address the related problems.
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The development of circularly polarized thermally activated delayed fluorescence (CP-TADF) luminogens with stimuli-response characteristics remains challenging. Herein, a pair of organic enantiomers, S-CzTA and R-CzTA, with aggregation-induced emission properties, have been successfully developed by introducing chiral 1,2,3,4-tetrahydronaphthalene and carbazole to phthalimide. They present CP-TADF properties in toluene solutions, giving dissymmetric factors of 0.84×10-3 and -1.03×10-3 , respectively. In the crystalline state, both S-CzTA and R-CzTA can emit intense blue TADF and produce very bright sky-blue mechanoluminescence (ML) and remarkable mechanofluorochromism (MFC) under the stimuli of mechanical force. Single-crystal analysis and theoretical calculation results suggest that their ML activities are probably associated with their chiral and polar molecular structures and unique non-centrosymmetric molecular packing modes. Furthermore, the MFC properties of the enantiomers likely originate from the destruction of crystal structure, leading to the planarization of molecular conformation. This work may provide helpful guidance for developing new CP-TADF materials with force-stimuli-responsive properties.
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Tetrahidronaftalenos , FluorescenciaRESUMEN
Color-tunable dual-mode organic afterglow excited by ultraviolet (UV) and white light was achieved from classical aggregation-caused quenching compounds for the first time. Specifically, two luminescent systems, which could produce significant organic afterglow composed of persistent thermally activated delayed fluorescence and ultralong organic phosphorescence under ambient conditions, were constructed by doping fluorescein sodium and calcein sodium into aluminum sulfate. Their lifetimes surpassed 600â ms, and the dopant concentrations were as low as 5×10-6 â wt %. Moreover, the persistent luminescence colors of the materials could be tuned from blue to green and then to yellow by simply varying the concentrations of guest compounds or the temperature in the range of 260-340â K. Inspired by these exciting results, the afterglow materials were used for UV- and white-light-manipulated anti-counterfeiting and preparation of elastomers with different colors of persistent luminescence.
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It remains a great challenge to develop polymer-based materials with efficient and color-tunable organic afterglow. Two indolocarbazole derivatives IaCzA and IbCzA have been synthesized and doped into poly(vinyl alcohol) (PVA) matrices. It is found that the resulting films can produce unique dual-mode afterglow, which is composed of persistent thermally activated delayed fluorescence and ultralong organic phosphorescence. Besides, the IbCzA-doped PVA film exhibits intense blue afterglow with Φafterglow and τafterglow up to 19.8 % and 1.81â s, respectively, representing state-of-the-art dual-mode organic afterglow performance. Moreover, our reported film has high flexibility, excellent transparency, and large-area producibility; and the afterglow color of the film can be linearly tuned by temperature. Inspired by these distinctive properties, the PVA doped with IbCzA was employed as temperature-sensitive security ink for anti-counterfeiting and information encryption.
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BACKGROUND: Gastric cancer (GC) has a poor prognosis and limited therapeutic options. As a new promising cancer therapeutic approach, chimeric antigen receptor (CAR)-T cells represent a potential GC treatment. We investigated the antitumor activity of CAR-T cells target-B7H3 in GC. METHODS: In our study, expression of B7H3 was examined in GC tissues and explored the tumoricidal potential of B7H3-targeting CAR-T cells in GC. B7H3-directed CAR-T cells with a humanized antigen-recognizing domain was generated. The anti-tumor effects of this CAR-T cell were finally investigated in vitro and in vivo. RESULTS: Our results show that B7H3-directed CAR-T cells efficiently killed GC tumor cells. In addition, we found that B7H3 is correlated with tumor cell stemness, and anti-B7H3 CAR-T can simultaneously target stem cell-like GC cells to improve the treatment outcome. CONCLUSIONS: Our study indicates that B7H3 is an attractive target for GC therapy, and B7H3 has high potential for clinical application.
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Fast fashion, as a continuously growing part of the textile industry, is widely criticized for its excessive resource use and high generation of textiles. To reduce its environmental impacts, numerous efforts are focused on finding sustainable and eco-friendly approaches to textile recycling. However, waste textiles and fibers are still mainly disposed of in landfills or by incineration after their service life and thereby pollute the natural environment, as there is still no effective strategy to separate natural fibers from chemical fibers. Herein, a green chemistry strategy is developed for the separation and regeneration of waste textiles at the molecular level. Cellulose/wool keratin composite fibers and multicomponent fibers are regenerated from waste textiles via a green chemical process. The strategy attempts to reduce the large amount of waste textiles generated by the fast-developing fashion industry and provide a new source of fibers, which can also address the fossil fuel reserve shortages caused by chemical fiber industries and global food shortages caused by natural fiber production.
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A pair of axially chiral organic enantiomers were facilely prepared through a one-pot sequential synthesis. They exhibit circularly polarized luminescence activities and have thermally activated delayed fluorescence (TADF) and aggregation-induced emission enhancement properties. Meanwhile, these two enantiomers present remarkable and reversible thermochromism in the crystalline state, enabling dual-colour TADF switching between orange and red. However, when they form cocrystals, the resulting racemate shows opposite thermochromic behaviors. These intriguing results probably emanate from their different optical activities, leading to distinct molecular packing modes and molecular conformation variations. Moreover, information encryption based on thermochromism of organic enantiomers and their racemate has been presented for the first time. This work may expand the application scope of chiral organic luminogens and pave a new way to construct intelligent luminescent systems.
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Stretchable electrical conductors have demonstrated promising potentials in a wide range of wearable electronic devices, but the conductivity of most reported stretchable conductive fibers will be changed if be stretched or strained. Stable conductance is essential for wearable and stretchable devices, to ensure the performance is stable. Inspired by the peristaltic behavior of arthropods, we designed a graphene coating similar to the caterpillar structure on the polyurethane (PU) fiber surface, enabled by coating the worm-shaped graphene microlayer onto polyurethane filaments. Such worm-shaped filaments can be stretched up to 1010% with a wide reversible electroresponse range (0 < ε < 815%), long-term durability (>4000 stretching/releasing cycles), good initial conductivity (σ0 = 124 S m-1), and high quality factor (Q = 11.26). Remarkably, the worm-shaped filaments show distinctive strain-insensitive behavior (ΔR/R0 < 0.1) up to 220% strain. Furthermore, the filaments as electrical circuits of light emitting diodes (LEDs) to track signals from robust human joint movements are also demonstrated for practical application. Such worm-shaped filaments with distinctive strain-insensitive behavior provide a direct pathway for stretchy electronics.
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Conductividad Eléctrica , Grafito/química , Nanotubos de Carbono/química , Dispositivos Electrónicos Vestibles , HumanosRESUMEN
Background: To investigate the clinical value of HE4 detection in the diagnosis of lung cancer and the clinical significance of combined detection with CEA, NSE and CYFRA21-1. Methods: 90 cases of lung cancer, 30 cases of pulmonary tuberculosis, 30 cases of pneumonia and 30 cases of health physical examination were selected. The levels of serum HE4, CYFRA21-1, CEA and NSE were detected by electrochemiluminescence method. Statistical analysis was performed to observe the sensitivity and specificity. Results: The levels of serum HE4, CEA, NSE and CYFRA21-1 in lung cancer group were significantly higher than those in tuberculosis group and health physical examination group. There was no significant difference in the levels of HE4, CEA and NSE between the lung cancer group and the pneumonia group, the difference of CYFRA21-1 level was statistically significant (p<0.05).With health physical examination group as normal controls, the sensitivity and specificity of combined detection of HE4, CEA, NSE and CYFRA21-1 in the diagnosis of lung cancer were 82.2% and 90.0%,and the area under the curve (AUC) was 0.907, followed by HE4 (0.867), CYFRA21-1 (0.787), CEA (0.752) and NSE (0.747). Conclusion: HE4 can be used as a serological marker for the diagnosis of lung cancer. The combined detection of HE4, CEA, NSE and CYFRA21-1 can improve the diagnosis of lung cancer. Serum HE4 levels are highly specific in distinguishing between lung cancer patients and normal population, and are equivalent to CYFRA21-1; but they are less specific than CYFRA21-1 in distinguishing lung cancer patients from pneumonia patients.
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Adenocarcinoma del Pulmón/diagnóstico , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP/análisis , Adenocarcinoma del Pulmón/sangre , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/sangre , Antígeno Carcinoembrionario/sangre , Carcinoma de Células Escamosas/sangre , Proteínas Portadoras/sangre , Estudios de Casos y Controles , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Queratina-19/sangre , Neoplasias Pulmonares/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Carcinoma Pulmonar de Células Pequeñas/sangreRESUMEN
BACKGROUND: Lentiviral vectors (LVs) have enhancer activity and/or transcriptional read-through (EATRT) properties that can lead to the activation of adjacent genes. Consequently, patients may be at increased risk for adverse effects if such vectors are used clinically. METHODS: In the present study, we assessed the abilities of different "pro-LV"-like constructs with respect to decreasing its EATRT, including the "pro-LV" vector bearing a chimeric ΔLTR of the human foamy virus R-U5 region replaced by that of an LV (HF). RESULTS: By analyzing the EATRT of "pro-LV" constructs transfected in 293T cells, we observed that the inclusion of the first 400 bp of the chicken ß-globin locus HS4 insulator core sequence oriented in the reverse direction (C-) combined with two copies of the simian virus 40 upstream-sequence element (U) at the ΔU3 of ΔLTR region of "pro-LV" tended to shield the adjacent genomic sequences, such that the EATRT rate was lower than when either of the C- or U was included in the "pro-LV". Moreover, upon transduction, the pro-HF appears to reduce the EATRT rate in the chromosomes of 293T (by 80%) and human peripheral blood mononuclear cells (PBMCs) (by 75%) compared to when pro-LV C-U was included (with a 60% and 89% reduction in 293T and PBMCs, respectively). The HF construct had a significant reduction of viral biological titer compared tiowhen the pro-LV C-U was used in 293T cells. CONCLUSIONS: The results of the present study provide an important basis for the clinical applicability of LVs in gene and cell therapy.
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Regulación de la Expresión Génica , Vectores Genéticos/genética , Interacciones Huésped-Patógeno/genética , Lentivirus/genética , Activación Transcripcional , Transducción Genética , Animales , Línea Celular , Orden Génico , Genes Reporteros , Humanos , Leucocitos Mononucleares/metabolismo , Ratones , Neuronas/metabolismo , Plásmidos/genética , Provirus/genética , TransgenesRESUMEN
PURPOSE: We sought to evaluate the activity and safety of these novel proteasome inhibitors (PIs) (carfilzomib, ixazomib, oprozomib and marizomib) containing regimens (single, doublet and triplet) for relapsed/refractory multiple myeloma (R/RMM). METHODS: We searched published reports including these novel PIs containing regimens for R/RMM. RESULTS: Finally, we identified 28 prospective studies that evaluated 4123 patients. Pooled analysis showed that novel PIs doublet combinations attained an impressive overall response rate (ORR) of 67%, which was higher than that of 22% from novel PIs single-agent (p < .001). And, the same trends favoring novel PIs doublet combinations were also shown in at least very good partial response (≥VGPR) and clinical benefit rate (CBR) analysis. Meanwhile, the ORR of 70% from novel PIs triplet regimens seemed to be similar to that of 67% from novel PIs doublet combinations (p = .54). And, there were no difference between them in ≥VGPR and CBR analysis. Compared to standard therapy, novel PIs combinations clearly benefited patients with R/RMM in terms of overall survival (HR, 0.79; p= .01), progression free survival(HR, 0.64; p = .01), overall response rate (RR = 1.21 p < .001). CONCLUSIONS: Novel PIs doublet combinations attained superior response outcomes over novel PIs single-agent in patients with R/RMM. Meanwhile, novel PIs triplet combinations had similar response outcomes with novel PIs doublet combinations. Compared to standard therapy, novel PIs combinations clearly prolonged survival for patients with R/RMM.