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In 1878, Lord Rayleigh observed the highly celebrated phenomenon of sound waves that creep around the curved gallery of St Paul's Cathedral in London1,2. These whispering-gallery waves scatter efficiently with little diffraction around an enclosure and have since found applications in ultrasonic fatigue and crack testing, and in the optical sensing of nanoparticles or molecules using silica microscale toroids. Recently, intense research efforts have focused on exploring non-Hermitian systems with cleverly matched gain and loss, facilitating unidirectional invisibility and exotic characteristics of exceptional points3,4. Likewise, the surge in physics using topological insulators comprising non-trivial symmetry-protected phases has laid the groundwork in reshaping highly unconventional avenues for robust and reflection-free guiding and steering of both sound and light5,6. Here we construct a topological gallery insulator using sonic crystals made of thermoplastic rods that are decorated with carbon nanotube films, which act as a sonic gain medium by virtue of electro-thermoacoustic coupling. By engineering specific non-Hermiticity textures to the activated rods, we are able to break the chiral symmetry of the whispering-gallery modes, which enables the out-coupling of topological 'audio lasing' modes with the desired handedness. We foresee that these findings will stimulate progress in non-destructive testing and acoustic sensing.
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Chimeric antigen receptor-T (CAR-T) cell has been developed as a promising agent for patients with refractory or relapsed lymphoma and leukemia, but not all the recipients could achieve a long-lasting remission. The limited capacity of in vivo expansion and memory differentiation post activation is one of the major reasons for suboptimal CAR-T therapeutic efficiency. Nitric oxide (NO) plays multifaceted roles in mitochondrial dynamics and T cell activation, but its function on CAR-T cell persistence and anti-tumor efficacy remains unknown. Herein, we found the continuous signaling from CAR not only promotes excessive NO production, but also suppressed S-nitrosoglutathione reductase (GSNOR) expression in T cells, which collectively led to increased protein S-nitrosylation, resulting in impaired mitochondrial fitness and deficiency of T cell stemness. Intriguingly, enforced expression of GSNOR promoted memory differentiation of CAR-T cell after immune activation, rendered CAR-T better resistance to mitochondrial dysfunction, further enhanced CAR-T cell expansion and anti-tumor capacity in vitro and in a mouse tumor model. Thus, we revealed a critical role of NO in restricting CAR-T cell persistence and functionality, and defined that GSNOR overexpression may provide a solution to combat NO stress and render patients with more durable protection from CAR-T therapy.
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Inmunoterapia Adoptiva , Mitocondrias , Receptores Quiméricos de Antígenos , Animales , Ratones , Mitocondrias/metabolismo , Receptores Quiméricos de Antígenos/metabolismo , Receptores Quiméricos de Antígenos/genética , Humanos , Inmunoterapia Adoptiva/métodos , Aldehído Oxidorreductasas/genética , Aldehído Oxidorreductasas/metabolismo , Linfocitos T/metabolismo , Linfocitos T/inmunología , Óxido Nítrico/metabolismo , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Activación de Linfocitos , Transducción de SeñalRESUMEN
Recurrence following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the major cause of treatment failure in patients with myeloid malignancy. Azacytidine (AZA) maintenance is a promising therapy to prevent relapse and improve survival. We conducted a prospective, one-arm study involving 78 patients with myeloid malignancy at a high risk of recurrence who were enrolled between September 2019 and April 2022. Furthermore, 102 matched historical controls were selected using propensity score matching. With a median follow-up time of 19.6 (3.5-91.7) months, AZA maintenance therapy significantly improved relapse-free survival (RFS; log-rank test, p = 0.01). The AZA and control groups had a 1-year RFS of 87.7% (95% confidence interval [CI], 0.80-0.96) and 72.2% (95% CI, 0.64-0.82), respectively, with a hazard ratio (HR) of 0.21 (95% CI, 0.09-0. 47; p < 0.01). There were no grade 4 adverse effects or deaths related to AZA. Refractory patients with favorable/intermediate-risk acute myeloid leukemia (AML) benefited more from AZA maintenance therapy than those with adverse-risk AML according to the European Leukemia Net guidelines (RFS in favorable/intermediate-risk AML, HR = 0.29, 95% CI, 0.11-0.79; RFS in adverse-risk AML, HR = 0.57, 95% CI, 0.21-1.6; p for interaction = 0.03). Our findings suggest that AZA maintenance therapy following allo-HSCT was safe and could reduce the incidence of relapse, particularly for refractory patients with favorable/intermediate-risk AML.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Azacitidina/uso terapéutico , Estudios Prospectivos , Trasplante Homólogo , Leucemia Mieloide Aguda/tratamiento farmacológico , Enfermedad Crónica , Recurrencia , Estudios RetrospectivosRESUMEN
Autologous hematopoietic stem cell transplantation (auto-HSCT), matched sibling donor HSCT (MSD-HSCT), and alternative donor HSCT (AD-HSCT) are viable post-remission treatment options for acute myeloid leukemia (AML). A total of 283 de novo favorable- and intermediate-risk AML patients, based on the ELN 2022 criteria, in first complete remission were initially included for propensity score matching. Following the matching process, 126 patients were selected for further analysis, with 42 patients in each of the auto-HSCT, MSD-HSCT, and AD-HSCT groups. Among the AD-HSCT group, 38 of 42 (90.5%) patients received haploidentical HSCT. In patients with persistent undetectable measurable residual disease (uMRD) before transplant (n = 83), overall survival (OS) was similar across the groups. However, auto-HSCT showed a trend of increased disease-free survival (DFS) compared to AD-HSCT (HR 2.85, P = 0.09), resulting in a 3-year DFS and OS of 79.1% and 82.8%, respectively. In the non-persistent uMRD group (n = 38), auto-HSCT exhibited a tendency to increase the risk of relapse, particularly when compared to AD-HSCT (HR 0.24, P = 0.07), but this did not result in inferior OS. The monthly direct medical cost per patient within the first 2 years after HSCT was significantly lower in auto-HSCT compared to MSD-HSCT (P = 0.015) and AD-HSCT (P < 0.001). Our results provide evidence for the use of auto-HSCT as a viable therapeutic option for favorable- and intermediate-risk de novo AML patients in first complete remission with persistent uMRD. Additionally, our findings demonstrated a notable cost advantage associated with auto-HSCT compared to MSD-HSCT and AD-HSCT.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Hermanos , Puntaje de Propensión , Donantes de Tejidos , Trasplante de Células Madre , Leucemia Mieloide Aguda/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Estudios RetrospectivosRESUMEN
Disease recurrence is the leading cause of treatment failure in patients with RUNX1::RUNXT1-positive acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Post-transplant maintenance therapy, guided by monitoring minimal residual disease (MRD), is commonly administered; however, relapse rates remain high. This prospective study aimed to assess the effectiveness and safety of epigenetic agents as prophylactic therapy in patients with RUNX1::RUNXT1-positive AML. Thirty high-risk patients received prophylactic therapy (n = 17 and n = 13 in the chidamide and AZA groups, respectively) between January 2019 and July 2023. 34 high-risk patients who received preemptive treatment due to molecular relapse were included in the analysis. The two-year relapse-free survival (RFS) and overall survival (OS) were significantly higher in the prophylactic group compared to the preemptive group (82.82% vs. 51.38%, P = 0.014; 86.42% vs. 56.16%, P = 0.025, respectively); 2-year cumulative incidence of relapse rates were 13.8% and 36.40%, respectively (P = 0.037). In conclusion, prophylactic therapy with epigenetic agents may improve long-term prognosis and is well-tolerated in patients with RUNX1::RUNXT1-positive high-risk AML. Timely post-transplant prophylactic therapy may be more effective than preemptive therapy based on positive MRD results.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal , Epigénesis Genética , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Femenino , Masculino , Persona de Mediana Edad , Adulto , Epigénesis Genética/efectos de los fármacos , Estudios Prospectivos , Proteína 1 Compañera de Translocación de RUNX1/genética , Benzamidas/uso terapéutico , Neoplasia Residual , Adulto Joven , Adolescente , Aloinjertos , Azacitidina/uso terapéutico , AminopiridinasRESUMEN
Wilms tumor 1 (WT1) gene mutations are infrequent in myelodysplastic syndrome (MDS), but MDS with WT1 mutations (WT1mut) is considered high risk for acute myeloid leukemia (AML) transformation. The influence of WT1 mutations in patients with MDS after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We performed a retrospective analysis of 136 MDS with excess blasts 2 (MDS-EB2) patients with available WT1 status who underwent their first allo-HSCT between 2017 and 2022 in our center. There were 20 (20/136, 15%) cases in the WT1mut group and 116 (116/136, 85%) cases in the WT1 wild-type (WT1wt) group. WT1mut patients had a higher 2-year cumulative incidence of relapse (CIR) than WT1wt cases (26.2% vs. 9.4%, p = 0.037) after allo-HSCT. Multivariate analysis of relapse showed that WT1 mutations (HR, 6.0; p = 0.002), TP53 mutations (HR, 4.2; p = 0.021), and ≥ 5% blasts in bone marrow (BM) at transplantation (HR, 6.6; p = 0.004) were independent risk factors for relapse. Patients were stratified into three groups according to the risk factors. Two-year CIR differed significantly in high-, intermediate-, and low-risk groups (31.8%, 11.6%, and 0%, respectively). Hence, WT1 mutations may be related to post-transplant relapse in patients with MDS-EB2, which warrants further study.
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Trasplante de Células Madre Hematopoyéticas , Mutación , Síndromes Mielodisplásicos , Proteínas WT1 , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Aloinjertos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/terapia , Síndromes Mielodisplásicos/etiología , Recurrencia , Estudios Retrospectivos , Proteínas WT1/genéticaRESUMEN
Adipose tissue CD11c+ myeloid cell is an independent risk factor associated with obesity and metabolic disorders. However, the underlying molecular basis remains elusive. Here, we demonstrated that liver kinase B1 (Lkb1), a key bioenergetic sensor, is involved in CD11c+ cell-mediated immune responses in diet-induced obesity. Loss of Lkb1 in CD11c+ cells results in obesity resistance but lower glucose tolerance, which accompanies tissue-specific immune abnormalities. The accumulation and CD80's expression of Lkb1 deficient adipose-tissue specific dendritic cells but not macrophages is restrained. Additionally, the balance of IL-17A and IFN-γ remarkably tips towards the latter in fat T cells and CD11c- macrophages. Mechanistically, IFN-γ promotes apoptosis of preadipocytes and inhibits their adipogenesis while IL-17A promotes the adipogenesis in vitro, which might account in part for the fat gain resistant phenotype. In summary, these findings reveal that Lkb1 is essential for fat CD11c+ dendritic cells responding to HFD exposure and provides new insights into the IL-17A/IFN-γ balance in HFD-induced obesity.
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Proteínas Quinasas Activadas por AMP , Intolerancia a la Glucosa , Resistencia a la Insulina , Obesidad , Animales , Ratones , Tejido Adiposo/metabolismo , Dieta Alta en Grasa/efectos adversos , Intolerancia a la Glucosa/metabolismo , Inflamación/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Obesidad/complicaciones , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Interferón gamma/metabolismoRESUMEN
The Su-Schrieffer-Heeger (SSH) model is an important cornerstone in modern condensed-matter topology, yet it is the simplest one-dimensional (1D) tight binding approach to dwell into the characteristics of spinless electrons in chains of staggered bonds. Moreover, the chiral symmetry assures that its surface-confining states pin to zero energy, i.e., they reside midgap in the energy dispersion. Symmetry is also an attribute related to artificial media that are subject to parity P and time-reversal T operations. This non-Hermitian family has been thoroughly nourished in a wave-based context, where anti-PT (APT) symmetric systems are the youngest belonging members, permitting refractionless optics, inverse PT-symmetry breaking transition, and asymmetric mode switching. Here, we report the first extension of APT symmetry in an acoustic setting by endowing a SSH lattice with gain and loss components. We show that the in-gap topological defect state hinges on the non-Hermitian phase, in that the broken symmetry suppresses it, yet when PT or APT symmetry is intact, it is observed with either damped or evanescent decay, respectively. Our experiments showcase how the non-Hermitian SSH lattice serves as a utile platform to investigate topological properties across various PT symmetric phases using sound.
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This prospective clinical investigation focused on the addition of venetoclax and decitabine to myeloablative conditioning regimens, targeting high-risk and elderly individuals undergoing allogeneic hematopoietic stem cell transplantation. In total, 19 patients were enrolled in the trial between December 2021 and February 2023, and their progress was monitored for a median follow-up period of 258 days, ranging from 35 to 544 days. In the initial regimen (n=11), venetoclax was administered at a dosage of 400 mg per day from day -14 to day -1, while in the modified regimen (n=8), it was administered from day -14 to day -5. Decitabine was orally administered at a dosage of 20mg/m2/day from day -7 to day -3. Grade 3/4 adverse events observed included hematological events, hypertension, infections, allergy, and increased amylase. In the entire cohort, the overall survival (OS) and relapse-free survival (RFS) rates at 6 months were 63% (95% CI, 45-89) and 63% (95% CI, 45-89), respectively. The non-relapse mortality (NRM) rate at 6 months was 37% (95% CI, 16-58), while the cumulative incidence of relapse (CIR) was 0. However, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD within 100 days was found to be 31% (95% CI, 12-53) and 26% (95% CI, 9-47), respectively. These rates indicate a relatively high occurrence, making it less suitable to administer the regimen to elderly patients. Therefore, further high-quality studies are required to enhance the conditioning regimen specifically for high-risk and elderly patients diagnosed with myeloid neoplasms. Clinical trial registration: ChiCTR2100050272.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trastornos Mieloproliferativos , Neoplasias , Humanos , Anciano , Decitabina , Estudios Prospectivos , Neoplasias/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trastornos Mieloproliferativos/complicaciones , Recurrencia , Acondicionamiento Pretrasplante/efectos adversos , Leucemia Mieloide Aguda/complicaciones , BusulfanoRESUMEN
The delayed platelet engraftment associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common complication and often results in increased transplant-related complications. A single-center, prospective, investigator-initiated pilot study was conducted to explore whether herombopag, a second generation thrombopoietin-receptor agonist, would promote platelet engraftment after allo-HSCT. Between 2/2022 and 06/2022, 17 individuals (median age 39; range 15-58 years) with hematological malignancies were enrolled. Herombopag was given for a median of 22 (range 14-61) days at a dose of 7.5 mg/d. The median time to neutrophil >500/µl was 11 (range 9-19) days. The median time to platelet >20 000/µl and >50 000/µl was 13 (range 8-22), and 20 (range 14-45) days, respectively. Compared with historical controls, the cumulative incidence of platelet engraftment after HSCT was significantly higher in the herombopag group (>20 000/µl at day +21, 88% vs 65%, p = .003; >50 000/µl at day +30, 65% vs. 43%, p = .001). Herombopag also reduced the units of platelet transfusion within 30 days post-SCT (3.6 ± 2.5 vs. 5.4 ± 3.2 U, p = .01). In conclusion, it seems likely that herombopag could enhance platelet engraftment after allo-HSCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto , Transfusión de Plaquetas/efectos adversos , Estudios Prospectivos , Proyectos Piloto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Plaquetas , Estudios RetrospectivosRESUMEN
BACKGROUND Transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) can improve the survival of patients with hepatocellular carcinoma (HCC). The purpose was to explore the characteristics of high-risk and low-risk groups of HCC patients receiving combination therapy using a decision tree model. MATERIAL AND METHODS This retrospective cohort study investigated HCC patients treated with a combination of TACE and RFA at our hospital from 2012 to 2018. Decision tree analysis was used to study the 1-year prognosis of patients, and patients were divided into high-risk and low-risk groups. RESULTS We included a total of 142 patients with HCC, 21.83% female and 78.17% male, with the median age of 60 years old. The median follow-up was 13.5 months; 39.44% of patients had progressive disease or death (high-risk group) and 60.56% of patients did not have progressive disease or survival (low-risk group). The area under the curve (AUC) of the decision tree model was 0.846. There were significant differences in sex (P=0.003), age (P=0.038), tumor number (P=0.043), number of RFAs in the first treatment cycle (P.
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Carcinoma Hepatocelular , Ablación por Catéter , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Ablación por Catéter/métodos , Quimioembolización Terapéutica/métodos , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Pinus sylvestris var. mongolica Litv. (Pinales: Pinaceae) is an excellent tree for soil and water conservation in Northeast China. The Honghua'erji area in Inner Mongolia is the "hometown of P. sylvestris var. mongolica", however, in recent years, coniferous diseases of P. sylvestris var. mongolica have frequently occurred here. During the investigation, it was found that some black spot needle blight had been observed in addition to the common blight caused by Sphaeropsis sapinea. From May to September 2020, black spot needle blight was found on hundreds of P. sylvestris var. mongolica trees in four forest farms, and the infection rate among the forests was 24.58 % (n=240). This disease first appeared on the upper part of the needles, and the needles then became withered and gradually showed light black spots, although they remained green. As the disease progressed, the needles eventually died and turned gray with many dark black spots. Fungal isolate named YJ-1 was obtained from infected needles of symptomatic pine trees, and a voucher specimen was deposited in Heilongjiang Province Key Laboratory of Forest Protection. Microscopic observation showed the conidia were 3-septate (4 cells) clavate spindles that measured 23.9 µm (20.8-25.9) × 5.9 µm (4.5-8.2) (n=50). The middle two cells were dark brown, and the septa were darker than the cells. Both apical and basal cells were hyaline. The apical cell had 2-4 appendages (mostly 3), and the basal cell had a truncate base (n=50). The cultural characteristics on potato dextrose agar medium were flat off-white and dense in 3-5 d. At approximately 5-7 d, the reverse side of the colony turned pale to slightly luteous. Superficial black acervuli were distributed in the center of the mature colonies after 10 d. Morphological, cultural and microscopic characteristics observed were similar of Heterotruncatella spartii (basionym: Truncatella spartii) reported by Hlaiem et al (2019). To further identify, total DNA was extracted and the internal transcribed spacer region (ITS-rDNA) was amplified by PCR using the primers ITS1/ITS4 and sequenced for BLASTn analysis and phylogenetic tree construction. The resulting 564 bp sequence (GenBank Accession No. OL662864) had 99.24% (521/525) to H. spartii MFLUCC 15-0537, with bootstrap support of at least 94% using the Neighbor-Joining algorithm by MEGA-X (Felsenstein, 1985). The fungus was identified as H. spartii based on morphology and molecular methods. A pathogenicity test was conducted by preparing a conidial suspension of 2.0 × 107 conidia/mL. The suspension was sprayed onto the needles of 20 pots of annual P. sylvestris ar. mongolica seedlings, and the control was sprayed with sterile water. Then the seedlings were placed in a constant temperature room at 25 °C. After 30 d, typical symptoms appeared on 11 inoculated needles, while the control needles remained symptomless. After 50 d, the re-isolation infection rate reached 66.7 %. The fungus present on the inoculated seedlings was morphologically identical to that originally observed on diseased pines, fulfilling Koch's postulates. The fungus was isolated from Spartium junceum for the first time and designated Truncatella spartii (Senanayake et al, 2015). It was then renamed H. spartii (Liu et al, 2019) and has been reported to infect P. pinea in Tunisia (Hlaiem et al, 2019). To our knowledge, this is the first report of H. spartii causing black spot needle blight on P. sylvestris var. mongolica in China and worldwide.
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BACKGROUND Hypertonic saline (HS) has been successfully used for treatment of various forms of brain edema. Decreased expression of aquaporin (AQP)4 and pro-inflammatory cytokines such as tumor necrosis factor (TNF)-a and interleukin (IL)-1b have been linked to edema pathogenesis. This study examined the effect of 3% HS on brain edema in a rat model of traumatic brain injury (TBI). MATERIAL AND METHODS Sprague-Dawley rats were subjected to TBI induced by a controlled cortical impactor. The HS group was injected with 3% NaCl until the end of the study period. AQP4, TNF-α, IL-1ß, and caspase-3 levels were measured by Western blotting, immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time PCR. Brain water content was also measured. Apoptotic cells in brain tissue were detected with terminal deoxynucleotidyl transferase dUTP nick-end labeling. Brain water content decreased following treatment with 3% HS relative to the TBI group. RESULTS This was accompanied by decreases in AQP4, TNF-α, and IL-1ß mRNA and protein levels. TBI resulted in increases in caspase-3 mRNA expression and the number of apoptotic cells; treatment with 3% HS suppressed apoptosis as compared to the TBI group. CONCLUSIONS Treatment with 3% HS ameliorated TBI-induced brain edema, possibly by suppressing brain edema, pro-inflammatory cytokine expression, and apoptosis.
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Acuaporina 4/metabolismo , Edema Encefálico/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Solución Salina Hipertónica/farmacología , Animales , Apoptosis/efectos de los fármacos , Acuaporina 4/genética , Edema Encefálico/metabolismo , Edema Encefálico/patología , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Caspasa 3/genética , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
PURPOSE: To prospectively evaluate safety and efficacy of biliary stent placement with iodine-125 (125I) seeds in patients with malignant obstructive jaundice (MOJ). MATERIALS AND METHODS: From July 2011 to June 2014, 55 patients were enrolled (group A, 11 men and 17 women, mean age 70.93 y ± 8.58; group B, 14 men and 13 women, mean age 70.26 y ± 9.71). All patients were randomly assigned to placement of a biliary stent with 125I seeds (group A) or biliary stent only (group B). After stent placement, outcomes were measured regarding relief of MOJ. Clinical success rate, survival time, and safety were recorded. P < .05 was considered to indicate significant difference. RESULTS: Stents were successfully placed in all 55 patients. MOJ was relieved in all patients, and there were no significant differences in complications related to stent insertion between the 2 groups. Mean and median stent patency were 191 days ± 19.8 (95% confidence interval [CI], 152-230 d) and 179 days ± 191.4 (95% CI, 87-267 d) in group A and 88.3 days ± 16.3 (95% CI, 61-114 d) and 77 days ± 88.2 (95% CI, 65-86 d) in group B (P < .001, log-rank test). Mean and median survival time were 222.6 days ± 21.0 (95% CI, 181-263 d) and 241 days ± 18.2 (95% CI, 179-270 d) in group A and 139.1 days ± 14.5 (95% CI, 110-167 d) and 142 days ± 16.3 (95% CI, 83-177 d) in group B (P < .001, log-rank test). CONCLUSIONS: 125I seeds combined with biliary stent placement could significantly improve stent patency. The procedure seems to be safe and to extend survival compared with self-expandable biliary stent placement.
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Braquiterapia , Colestasis/terapia , Neoplasias del Sistema Digestivo/complicaciones , Radioisótopos de Yodo/administración & dosificación , Ictericia Obstructiva/terapia , Stents Metálicos Autoexpandibles , Anciano , Anciano de 80 o más Años , Aleaciones , Braquiterapia/efectos adversos , China , Colestasis/diagnóstico por imagen , Colestasis/etiología , Colestasis/mortalidad , Neoplasias del Sistema Digestivo/diagnóstico por imagen , Neoplasias del Sistema Digestivo/mortalidad , Femenino , Humanos , Radioisótopos de Yodo/efectos adversos , Ictericia Obstructiva/diagnóstico por imagen , Ictericia Obstructiva/etiología , Ictericia Obstructiva/mortalidad , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Radiografía Intervencional , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
To compare the ABZ and its metabolites concentration in cyst tissue of hepatic alveolar echinococcosis administered by different routes, forty male Wistar rats receiving albendazole nanoparticles from tail vein and portal vein were divided into two groups, the concentration of ABZ and its metabolites ABZSO, ABZSO2, in the cyst tissue, were analyzed by HPLC at 2, 4, 8, 24, 36 h after administration. The parent drug and its metabolites were detected in plasm and the cyst tissue after portal cannulation and intravenous administration. The last results were the concentration of ABZ in the portal cannulation group was higher than in the intravenous group at every time point (p < 0.05). Compared to the intravenous group, the portal cannulation administration of ABZ led to a lower plasm concentration of ABZ. The concentration of ABZ and the active ABZSO were significantly higher in the portal cannulation group than that of the intravenous group.
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Albendazol/administración & dosificación , Anticestodos/administración & dosificación , Equinococosis Hepática/tratamiento farmacológico , Nanopartículas/administración & dosificación , Albendazol/farmacocinética , Animales , Anticestodos/farmacocinética , Cateterismo , Equinococosis Hepática/metabolismo , Inyecciones Intravenosas , Masculino , Ratones , Nanopartículas/metabolismo , Vena Porta , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
This study is aimed to investigate the effect of serum vascular endothelial growth factor (VEGF) levels on prognosis of hepatocellular carcinoma (HCC) patients receiving radiofrequency ablation (RFA). The 110 HCC patients who received computed tomography (CT) guided RFA were enrolled in this study. The levels of serum VEGF were determined before and after RFA by enzyme-linked immunosorbent assay (ELISA). According to the ELISA results, the patients were divided into the negative group and the positive group. The patient's progression-free survival time was determined. It was demonstrated that the serum VEGF had no significant correlation with ages, sex and tumour size. There were no significant peripheral blood supplies around tumour necrosis. The results showed that higher levels of serum VEGF had a worse prognosis when compared to the patients with lower levels of serum VEGF. The difference between the area under the receiver operating characteristic curve and those when area under curves equalled 0.5 was statistically significant (P < 0.05). The serum VEGF level in liver cancer patients can be used as a prognostic indicator for evaluating the efficacy of RFA treatments.
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OBJECTIVE: To observe the morphological change in the pathological process of Echinococcus multilocularis in liver of infected rats after treatment with liposome entrapped albendazole and iodized oil suspension through portal vein, and investigate its efficacy against hepatic alveolar echinococcosis. METHODS: One Echinococcus multilocularis-infected rat served as control. Another 19 infected rats were infused with 0.2ml liposome entrapped albendazole and iodized oil suspension through portal vein. At 4, 7 and 10 d after treatment, the rats were sacrificed for further observation. The E. multilocularis metacestodes were collected, and the pathological change of alveolar hydatid was observed with hematoxylin-eosin staining and toluidine blue staining. RESULTS: In four days post treatment, E. multilocularis metacestodes were normal On the 7th day and 10th day post treatment, the major pathological change was degeneration and necrosis, respectively. A great quantity of liposomes and iodized oil deposited in the metacestodes, and caused breakdown of E. multilocularis tissue, collapse of cysts, cataplasia of germinal layer and laminated layer. CONCLUSION: Interventional therapy trans-hepatic vein may be an effective way to treat hepatic alveolar echinococcosis.
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Equinococosis Hepática/patología , Echinococcus multilocularis , Vena Porta/patología , Albendazol , Animales , Equinococosis Hepática/terapia , Embolización Terapéutica , Necrosis , RatasRESUMEN
BACKGROUND: Enhanced magnetic resonance imaging (MRI) is widely used in the diagnosis, treatment and prognosis of hepatocellular carcinoma (HCC), but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment. Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival (PFS). AIM: To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images. METHODS: Delineate the regions of interest (ROI) in arterial phase, portal venous phase and delayed phase of enhanced MRI. After extracting the combinatorial features of ROI, the features are fused to obtain deep learning radiomics (DLR)_Sig. DeLong's test was used to evaluate the diagnostic performance of different typological features. K-M analysis was applied to assess PFS in different risk groups, and the discriminative ability of the model was evaluated using the C-index. RESULTS: Tumor diameter and diolame were independent factors influencing the prognosis of PFS. Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases (P < 0.05).In deep transfer learning (DTL) and DLR, significant differences were observed between the multi-phase and individual phases feature sets (P < 0.05). K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months, respectively, and the predicted probabilities of 6 months, 1 year and 2 years were 92%, 60%, 40% and 98%, 90%,73%, respectively. The C-index was 0.764, indicating relatively good consistency between the predicted and observed results. DTL and DLR have higher predictive value for 2-year PFS in nomogram. CONCLUSION: Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph, it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC.
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Background: Since the introduction of drug-eluting beads (DEB), the result comparing transarterial chemoembolization (TACE) using lipiodol, also called conventional transarterial chemoembolization (c-TACE), and DEB-TACE shows considerable controversy. The objective of this study was to compare the safety and efficacy of c-TACE and DEB-TACE to treat unresectable hepatocellular carcinoma (uHCC). Methods: This retrospective study used propensity score matching (PSM) analysis to analyze clinical data from 113 cases of primary hepatocellular carcinoma (HCC) treated at our hospital from September 2016 to July 2021. The safety and efficacy of the two treatment modalities were analyzed after 1:1 matching. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS), disease control rates (DCRs), and objective response rates (ORRs) at 1, 3, 6, and 12 months, and postoperative complications. Results: Twenty-nine patients underwent DEB-TACE and 84 received c-TACE; 28 pairs of patients were eventually matched. After matching, baseline characteristics between groups were comparable. The median PFS of the DEB-TACE group was 10 months compared to 6 months in the c-TACE group (P=0.002). The median OS was 23 months in the DEB-TACE group vs. 14 months in the c-TACE group, but the difference was not statistically significant (P=0.265). The ORR at 1, 3, 6, and 12 months in the DEB-TACE group (69%, 78%, 60%, and 52%) were significantly higher than those in the c-TACE group (39%, 39%, 26%, and 8%) (P<0.05). The DCR at postoperative 3 months was significantly higher in the DEB-TACE group (95%) (P<0.05). There was one case of postoperative liver abscess in the DEB-TACE group, and the patient recovered well after drainage. No serious complications occurred. Conclusions: Compared to c-TACE, DEB-TACE prolonged PFS and exhibited better short-term ORR with a similar level of safety. However, there was no significant advantage in terms of OS.
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Bone marrow fibrosis (BMF) of unknown etiology was common in hematological malignancies, but its prognostic value for acute myeloid leukemia (AML) is unclear. We interrogated data from 532 newly diagnosed subjects with AML receiving allogeneic hematological stem cell transplantation to evaluate the prognostic impact of BMF on transplant outcomes. Using the European consensus on the grading of BMF at diagnosis, 255 (48%) subjects were BMF-0, 209 (39%), BMF-1 and 68 (13%), BMF-2-3. Subjects with BMF-2-3 had poor overall survival (P < 0.001), disease-free survival (P < 0.001) and a higher incidence of relapse (CIR, P < 0.001). Multi-variable analyses in subjects achieving pre-transplant complete remission showed BMF-2-3 was an independent risk factor for CIR (Hazard Ratio [HR] = 2.17, (95% CI, 1.11, 4,24); P = 0.02). Furthermore, BMF-2-3 group showed delayed neutrophil and platelet engraftment and delayed B cell recovery post-transplantation. These findings demonstrate the significance of BMF in transplant outcomes and attract more attention to AML with BMF.