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In this study, we used the whole-exome sequencing (WES) approach to obtain genomic profiles from 92 marrow samples of myelodysplastic syndrome (MDS) patients before haematopoietic stem cell transplantation. We identified 129 mutations in 45 driver genes. Fifty-five patients (59.8%) carried at least 1 driver mutation. The splicing factor U2AF1 was the most frequently mutated in the cohort (21 cases, 23%), followed by BCOR (9 cases, 10%), ASXL1 (8 cases, 9%), TET2 (6 cases, 7%), NPM1 (5 cases, 5%), RUNX1 (5 cases, 5%), and SETBP1 (5 cases, 5%). WES also identified 49 possible oncogenic variants in six genes (PIEZO1, LOXHD1, MYH13, DNAH5, DPH1, and USH2A) that were associated with overall survival (OS) or relapse-free survival (RFS) in MDS after transplantation. Multivariate analysis showed mutations in DNAH5 and USH2A to be independent risk factors for OS. Mutations in DNAH5 and LOXHD1 were risk factors for worse RFS. The Molecular International Prognostic Scoring System retained its independent prognostic significance for RFS after multivariate analysis.
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Cordyceps cicadae is recognized for its medicinal properties, attributed to bioactive constituents like polysaccharides and adenosine, which have been shown to improve kidney and liver functions and possess anti-tumor properties. Rho GTPase activating proteins (Rho GAPs) serve as inhibitory regulators of Rho GTPases in eukaryotic cells by accelerating the GTP hydrolysis of Rho GTPases, leading to their inactivation. In this study, we explored the function of the CcRga8 gene in C. cicadae, which encodes a Rho-type GTPase activating protein. Our study found that the knockout of CcRga8 resulted in a decrease in polysaccharide levels and an increase in adenosine concentration. Furthermore, the mutants exhibited altered spore yield and morphology, fruiting body development, decreased infectivity, reduced resistance to hyperosmotic stress, oxidative conditions, and cell wall inhibitors. These findings suggest that CcRga8 plays a crucial role in the development, stress response, and bioactive compound production of C. cicadae.
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Cordyceps , Cordyceps/metabolismo , Cordyceps/genética , Cordyceps/crecimiento & desarrollo , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Activadoras de GTPasa/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Adenosina/metabolismo , Polisacáridos/metabolismo , Cuerpos Fructíferos de los Hongos/crecimiento & desarrollo , Cuerpos Fructíferos de los Hongos/metabolismo , Cuerpos Fructíferos de los Hongos/genéticaRESUMEN
Bacterial cellulose (BC) hydrogel is renowned in the field of tissue engineering for its high biocompatibility, excellent mechanical strength, and eco-friendliness. Herein, we present a biomimetic mineralization method for preparing BC/hydroxyapatite (HAP) composite hydrogel scaffolds with different mineralization time and ion concentration of the mineralized solution. Spherical HAP reinforcement enhanced bone mineralization, thereby imparting increased bioactivity to BC matrix materials. Subsequently, platelet-rich plasma (PRP) was introduced into the scaffold. The PRP-loaded hydrogel enhanced the release of growth factors, which promoted cell adhesion, growth, and bone healing. After 3 weeks of MC3T3-E1 cell-induced osteogenesis, PRP positively affected cell differentiation in BC/HAP@PRP scaffolds. Overall, these scaffolds exhibited excellent biocompatibility, mineralized nodule formation, and controlled release in vitro, demonstrating great potential for application in bone tissue repair.
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Celulosa , Durapatita , Hidrogeles , Osteogénesis , Plasma Rico en Plaquetas , Ingeniería de Tejidos , Andamios del Tejido , Plasma Rico en Plaquetas/química , Ingeniería de Tejidos/métodos , Durapatita/química , Durapatita/farmacología , Celulosa/química , Celulosa/farmacología , Animales , Ratones , Andamios del Tejido/química , Hidrogeles/química , Osteogénesis/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/metabolismo , Preparaciones de Acción Retardada/farmacología , Diferenciación Celular/efectos de los fármacos , Biomimética/métodos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Línea Celular , Regeneración Ósea/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVE: Calcaneal Sanders type II or III fractures are highly disabling with significant burden. Surgical treatment modalities include open reduction and internal fixation (ORIF) techniques and a variety of minimally invasive surgical (MIS) approaches. ORIF techniques are associated with complications and traditional MIS techniques need extensive intraoperative fluoroscopic procedures. The present study aims to investigate the effects of three different minimally invasive internal fixation (MIIF) techniques used to treat Sanders type II intra-articular calcaneal fractures using finite element analyses. METHODS: A 64-row spiral computed tomography scan was used to observe the calcaneus of a healthy adult. The scanning data were imported into Mimics in a DICOM format. Using a new model of a Sanders type II-B intra-articular calcaneal fracture, three minimally invasive techniques were simulated. Technique A involved fixation using an isolated minimally invasive locking plate; Technique B used a minimally invasive locking plate with one medial support screw; and Technique C simulated a screw fixation technique using four 4.0-mm screws. After simulating a 640-N load on the subtalar facet, the maximum displacement and von Mises stress of fragments and implants were recorded to evaluate the biomechanical stability of different fixation techniques using finite element analyses. RESULTS: After stress loading, the maximum displacements of the fragments and implants were located at the sustentaculum tali and the tip of sustentaculum tali screw, respectively, in the three techniques; however, among the three techniques, Technique B had better results for displacement of both. The maximum von Mises stress on the fragments was < 56 Mpa, and stress on the implants using the three techniques was less than the yield strength, with Technique C having the least stress. CONCLUSION: All three techniques were successful in providing a stable fixation for Sanders type II intra-articular calcaneal fractures, while the minimally invasive calcaneal locking plate with medial support screw fixation approach exhibited greater stability, leading to improved enhancement for the facet fragment; however, screw fixation dispersed the stress more effectively than the other two techniques.
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Traumatismos del Tobillo , Calcáneo , Traumatismos de los Pies , Fracturas Óseas , Fracturas Intraarticulares , Adulto , Humanos , Análisis de Elementos Finitos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Pie , Fijación Interna de Fracturas/métodos , Calcáneo/diagnóstico por imagen , Calcáneo/cirugía , Tornillos Óseos , Placas Óseas , Fracturas Intraarticulares/diagnóstico por imagen , Fracturas Intraarticulares/cirugía , Resultado del TratamientoRESUMEN
Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent. We reviewed 108 patients with hematological diseases including acute leukemia, myelodysplastic syndrome, aplastic anemia, and others who received allogeneic hematopoietic stem cell transplantation (HSCT) from January 2019 through December 2020. After multivariable logistic regression, we found that splenomegaly (odds ratio [OR] = 26.98, p < .001) and JAK mutation (OR = 17.32, p = .024) were independent risk factors for PTR. During the period of transplantation, patients in the PTR group had a significantly higher platelet transfusion demand, which was reflected in the increased number of platelet transfusions (10.23 ± 6.696 vs. 5.06 ± 1.904, p < .001). After multivariate adjustment, PTR turned out to be independently associated with worse overall survival (hazard ratio = 2.794, 95% confidence interval = 1.083-7.207, p = .034). In conclusion, we found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. A history of PTR prior to allo-HSCT indicates a poor prognosis.
What is the context?Platelet transfusion refractoriness is a critical issue, and it greatly increases bleeding risks and hospitalization costs.Patients with hematological diseases tend to develop PTR.PTR results from immune and nonimmune factors and the latter account for 8090%.At present, there are few studies focused on the inducing factors of PTR, and the specific mechanism is not clear.What is new?In this study, we investigated 108 patients with hematological disorders who received allogeneic HSCT from January 2019 to December 2020.We found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases.PTR had a passive effect on the prognosis of patients after HSCT, as indicated by worse OS and a trend toward lower platelets after transplantation.PTR might affect megakaryocyte reconstitution after transplantation.What is the impact?This study provides evidence that hematological patients with splenomegaly should be alert to the occurrence of PTR, which often indicates a worse prognosis of transplantation.Spleen reduction and JAK inhibitors in the treatment of PTR are worth exploring.AbbreviationsPLT: platelets; PTR: platelet transfusion refractoriness; HSCT: hematopoietic stem cell transplantation; OR: odds ratio; HR: hazard ratio; CI: confidence interval; IQR: interquartile range; SD: standard deviation; HLA: human leukocyte antigen; HPA: human platelet antigen; OS: overall survival; RFS: relapse free survival; PI: post-transfusion increment; PPR: percentage platelet recovery; CCI: corrected count increment; ICU: intensive care unit; AA: aplastic anemia; MDS: myelodysplastic syndrome; AML: acute myeloid leukemia; ALL: acute lymphocytic leukemia; CML: chronic myeloid leukemia; CMML: chronic myelomonocytic leukemia; MPN: myeloproliferative neoplasm; SI: splenic irradiation; Abs: antibodies; CR: complete remission; DAC: decitabine; GVHD: graft-versus-host disease; BM: bone marrow; PB: peripheral blood.
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Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Humanos , Estudios Retrospectivos , Transfusión de Plaquetas/efectos adversos , Esplenomegalia/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Pronóstico , Síndromes Mielodisplásicos/terapia , Factores de RiesgoRESUMEN
Hepatitis B virus (HBV) infection is a noteworthy cause of liver diseases, especially cirrhosis and hepatocellular carcinomas. However, the interaction between the host and HBV has not been fully elucidated. Peptide YY (PYY) is a 36-amino-acid gastrointestinal hormone that is mainly involved in the regulation of the human digestive system. This study found that PYY expression was reduced in HBV-expressing hepatocytes and HBV patients. Overexpression of PYY could significantly inhibit HBV RNA, DNA levels, and the secretion of HBsAg. In addition, PYY inhibits HBV RNA dependent on transcription through reducing the activities of CP/Enh I/II, SP1 and SP2. Meanwhile, PYY blocks HBV replication independent on core, polymerase protein and ε structure of pregenomic RNA. These results suggest that PYY can impair HBV replication by suppressing viral promoters/enhancers in hepatocytes. Our data shed light on a novel role for PYY as anti-HBV restriction factor.
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Hepatitis B , Neoplasias Hepáticas , Humanos , Virus de la Hepatitis B/genética , Péptido YY , Replicación Viral/genética , Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/genética , ARNRESUMEN
The damage or degeneration of spiral ganglion neurons (SGNs) can impair the auditory signals transduction from hair cells to the central auditory system, and cause significant hearing loss. Herein, a new form of bioactive hydrogel incorporating topological graphene oxide (GO) and TEMPO-oxidized bacterial cellulose (GO/TOBC hydrogel) was developed to provide a favorable microenvironment for SGN neurite outgrowth. As the network structure of lamellar interspersed fiber cross-linked by GO/TOBC hydrogels well simulated the structure and morphology of ECM, with the controllable hydrophilic property and appropriate Young's modulus well met those requirements of SGNs microenvironment, the GO/TOBC hybrid matrix exhibited great potential to promote the growth of SGNs. The quantitative real-time PCR result confirmed that the GO/TOBC hydrogel can significantly accelerate the development of growth cones and filopodia, by increasing the mRNA expression levels of diap3, fscn2, and integrin ß1. These results suggest that GO/TOBC hydrogel scaffolds have the potential to be used to construct biomimetic nerve grafts for repairing or replacing nerve defects.
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Celulosa Oxidada , Ganglio Espiral de la Cóclea , Ganglio Espiral de la Cóclea/metabolismo , Hidrogeles/química , Neuronas/metabolismoRESUMEN
BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy. Several studies have demonstrated the efficacy of caplacizumab in iTTP. However, the effect on different populations remains controversial. Therefore, we performed a systematic review and meta-analysis to assess the effectiveness and safety of caplacizumab for treating iTTP. MATERIALS AND METHODS: We searched PubMed, Embase, and the Cochrane Library for studies until 24 March 2023. Participants were hospitalized patients with iTTP. Interventions included caplacizumab versus placebo or standard of care (SOC). Outcomes assessed included all-cause mortality, exacerbation, relapse, refractory, time-to-platelet-count-recovery, length of TPE and hospital stay, bleeding, and thrombosis. RESULTS: A total of 1119 patients from eight studies were subjected to meta-analysis. The results of the meta-analysis showed that iTTP patients treated with caplacizumab achieved a reduction in mortality (RR 0.38, 95% CI: 0.19-0.75), exacerbation (RR 0.29, 95% CI: 0.14-0.61) and refractory (RR 0.50, 95% CI: 0.31-0.81). Besides, adding caplacizumab to SOC was associated with a shorten time-to-platelet-count-recovery (MD - 2.31, 95% CI: -3.86 to -0.77) and length of TPE (MD - 4.61, 95% CI: -6.20 to -3.02). In terms of safety, the bleeding rate was higher in the caplacizumab group (RR 1.57, 95% CI: 1.21-2.02), while there was no significant difference in hospital stay and thrombosis between the two groups. CONCLUSIONS: Caplacizumab is an effective treatment for patients with iTTP, especially in reducing all-cause mortality, exacerbations, refractoriness, and the time-to-platelet-count-recovery. Although the risk of bleeding may be increased, it is generally modest and manageable.
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Púrpura Trombocitopénica Trombótica , Anticuerpos de Dominio Único , Humanos , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Hemorragia/terapia , Anticuerpos de Dominio Único/uso terapéutico , Intercambio PlasmáticoRESUMEN
Purpose: Appropriate pre-transplant strategies in patients with myelodysplastic syndromes (MDS) remain challenging. We sought to assess the effect of different pre-transplant therapies and transplantation interval times on patient prognosis. Methods: We retrospectively analysed clinical data for 371 consecutive MDS patients after myeloablative transplantation between 2007 and 2019. Results: The median age of the patients was 38 years (range, 12-64 years). A total of 114 patients (31%) received supportive care (SC), 108 (29%) hypomethylating agents (HMAs), and 149 (40%) chemotherapy-based therapy before transplantation. In patients who received HMA or SC, there was no significant difference in overall survival (OS; P=0.151) or relapse-free survival (RFS; P=0.330), except that HMA-treated patients had a lower rate of non-relapse mortality (5-year NRM: 18% vs. 32%, P=0.035). However, compared with patients who received HMA, those who received chemotherapy-based therapy had a lower 5-year OS rate (56% vs. 69%, P=0.020) and a slightly higher 5-year NRM rate (28% vs. 18%, P=0.067). Compared to the delayed transplant group (transplant interval ≥6 months), the early transplant group (transplant interval <6 months) had a superior 5-year OS (66% vs. 51%, P=0.001) and a lower 5-year cumulative incidence of NRM (22% vs. 36%, P=0.001). Conclusion: The findings of the study indicate that receiving an appropriate pre-transplant strategy (SC/HMA + <6 months) significantly improves OS and decreases NRM in MDS patients after myeloablative transplantation.
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Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndromes Mielodisplásicos/tratamiento farmacológico , PronósticoRESUMEN
BACKGROUND: Chronic ankle instability (CAI) is a common sequela following an acute lateral ankle sprain (LAS). To treat an acute LAS more effectively and efficiently, it is important to identify patients at substantial risk for developing CAI. This study identifies magnetic resonance imaging (MRI) manifestations for predicting CAI development after a first episode of LAS and explores appropriate clinical indications for ordering MRI scans for these patients. METHODS: All patients with a first-episode LAS who received plain radiograph and MRI scanning within the first 2 weeks after LAS from December 1, 2017 to December 1, 2019 were identified. Data were collected using the Cumberland Ankle Instability Tool at final follow-up. Demographic and other related clinical variables, including age, sex, body mass index, and treatment were also recorded. Univariable and multivariable analyses were performed successively to identify risk factors for CAI after first-episode LAS. RESULTS: A total 131 out of 362 patients with a mean follow-up of 3.0 ± 0.6 years (mean ± SD; 2.0-4.1 years) developed CAI after first-episode LAS. According to multivariable regression, development of CAI after first-episode LAS was associated with 5 prognostic factors: age (odds ratio (OR)â¯=â¯0.96, 95% confidence interval (95%CI): 0.93-1.00, pâ¯=â¯0.032); body mass index (ORâ¯=â¯1.09, 95%CI: 1.02-1.17, pâ¯=â¯0.009); posterior talofibular ligament injury (ORâ¯=â¯2.17, 95%CI: 1.05-4.48, pâ¯=â¯0.035); large bone marrow lesion of the talus (ORâ¯=â¯2.69, 95%CI: 1.30-5.58, pâ¯=â¯0.008), and Grade 2 effusion of the tibiotalar joint (ORâ¯=â¯2.61, 95%CI: 1.39-4.89, pâ¯=â¯0.003). When patients had at least 1 positive clinical finding in the 10-m walk test, anterior drawer test, or inversion tilt test, they had a 90.2% sensitivity and 77.4% specificity in terms of detecting at least 1 prognostic factor by MRI. CONCLUSION: MRI scanning is valuable in predicting CAI after first-episode LAS for those patients with at least 1 positive clinical finding in the 10-m walk test, anterior drawer test, and inversion tilt test. Further prospective and large-scale studies are necessary for validation.
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Traumatismos del Tobillo , Inestabilidad de la Articulación , Humanos , Articulación del Tobillo/diagnóstico por imagen , Tobillo , Estudios Retrospectivos , Factores de Riesgo , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/etiología , Traumatismos del Tobillo/diagnóstico por imagen , Traumatismos del Tobillo/complicacionesRESUMEN
BACKGROUND: Platelet transfusion refractoriness (PTR) remains an intractable issue in clinical practice, and is common in hematological patients. At present, it is believed that both immune and non-immune factors play a role. We conducted a meta-analysis of various risk factors which may contribute to PTR. METHODS: PubMed, Embase, Cochrane library, and Web of Science were selected as research database platforms. Citations included were further assessed for quality and bias using the Newcastle-Ottawa Scale. All analyses were performed using Review Manager Version 5.4 and STATA 16.0. RESULTS: The preliminary search revealed 1069 publications, and 17 (5929 patients in total) were ultimately included in the quantitative analysis. The following variables were associated with the occurrence of PTR: fever (OR = 2.26, 95%CI 2.00-2.55, p < 0.00001), bleeding (OR = 2.10, 95%CI 1.36-3.24, p = 0.0008), female sex (OR = 2.06, 95%CI 1.13-3.75, p = 0.02), antibiotic use (OR = 2.94, 95%CI 1.54-5.59, p = 0.001), and infection (OR = 2.19, 95%CI 1.20-4.03, p = 0.01). Antibodies involved in immune activation were a higher risk factor (OR = 4.17, 95%CI 2.36-7.36, p < 0.00001), and splenomegaly was nearly significant (OR = 1.73, 95%CI 0.97-3.07, p = 0.06). CONCLUSIONS: We identified some important risk factors for PTR, but further research is needed to identify the many other possible elements that may contribute to or mediate PTR.
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Transfusión de Plaquetas , Trombocitopenia , Humanos , Femenino , Transfusión de Plaquetas/efectos adversos , Trombocitopenia/etiología , Hemorragia/etiología , Factores de RiesgoRESUMEN
PURPOSE: The aim of this study was to evaluate the relation between anteromedial ankle osteophytes (AMAO) and anteromedial ankle impingement (AMAI) in chronic lateral ankle instability (CLAI) through visualization and quantification. METHODS: Forty-three patients with unilateral CLAI between September 2018 and March 2020 accepted arthroscopic repair of an anterior talofibular ligament (ATFL) and were split into two groups: AMAI (AMAI including intraoperative AMAO resection) and pure CLAI (with AMAO but without AMAI, no AMAO resection). The AMAO protrusion lengths in each direction were measured and compared after all of the ankles were reconstructed. All patients were assessed preoperatively and at 2-year follow-up with ankle dorsiflexion, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and visual analog scale (VAS) score. RESULTS: Intelligent analysis showed that a large extent of osteophytes was found at the dorsomedial surface of the talar neck in AMAI group. The upper and inner bound protrusion distances of AMAO in AMAI group were greater than in the pure CLAI group. There was no significant difference in anterior bound protrusion distance of AMAO between the two groups. Preoperatively, the ankle dorsiflexion of AMAI group (7.6 ± 1.4°) was considerably lower than that of pure CLAI group (22.4 ± 1.9°) (p < 0.001). When compared to the pure CLAI group, the AMAI group had a substantially worse AOFAS score (62.2 ± 6.7 vs 71.1 ± 9.1; p < 0.001) and VAS score (6.0 ± 1.0 vs 4.9 ± 0.8; p < 0.05). However, there was no significant difference in postoperative ankle dorsiflexion, AOFAS score, or VAS score between the two groups. CONCLUSION: AMAO is formed mostly on the dorsomedial surface of the talar neck in CLAI with AMAI, and the upper and inner bound protrusion lengths of AMAO were shown to be significantly correlated with the existence of AMAI in CLAI.
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Inestabilidad de la Articulación , Osteofito , Astrágalo , Humanos , Tobillo , Relevancia Clínica , Articulación del TobilloRESUMEN
In this work, the effects of konjac glucomannan (KGM) concentrations on microstructure, gel properties, stability and digestibility of water-in-oil-in-water emulsion gels stabilized by polyglycerol polyricinoleate and whey protein isolate were investigated. Visual appearance indicated that a non-layered double emulsion gel was formed when KGM increased to 0.75%. Emulsion gels with 1.5% KGM showed the highest encapsulation, freeze-thaw and photochemical stability due to the formation of the smallest droplets, which were supported by microscopic observations. Moreover, the addition of KGM improved water holding capacity, rheological and texture properties of emulsion gels. Particularly, at 1.5% or 1.75% KGM, color and potential of hydrogen showed the most stable level after 14 days of storage. During in vitro digestion, KGM delayed the hydrolysis of protein and oil droplets, and then improved the bioavailability of grape seed proanthocyanidin. These results promoted the application of KGM in emulsion gels and the encapsulation of nutraceuticals.
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Digestión , Agua , Emulsiones/química , Proteína de Suero de Leche , Geles/química , Agua/químicaRESUMEN
BACKGROUND: DNA methylation is a form of epigenetic modification that regulates gene expression. However, there are limited data on the comprehensive analysis of DNA methylation regulated gene mutations (DMRGM) in acute myeloid leukemia (AML) mainly referring to DNA methyltransferase 3α (DNMT3A), isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2), and Tet methylcytidine dioxygenase 2 (TET2). RESULTS: A retrospective study of the clinical characteristics and gene mutations in 843 newly diagnosed non-M3 AML patients was conducted between January 2016 and August 2019. 29.7% (250/843) of patients presented with DMRGM. It was characterized by older age, higher white blood cell count, and higher platelet count (P < 0.05). DMRGM frequently coexisted with FLT3-ITD, NPM1, FLT3-TKD, and RUNX1 mutations (P < 0.05). The CR/CRi rate was only 60.3% in DMRGM patients, significantly lower than in non-DMRGM patients (71.0%, P = 0.014). In addition to being associated with poor overall survival (OS), DMRGM was also an independent risk factor for relapse-free survival (RFS) (HR: 1.467, 95% CI: 1.030-2.090, P = 0.034). Furthermore, OS worsened with an increasing burden of DMRGM. Patients with DMRGM may be benefit from hypomethylating drugs, and the unfavorable prognosis of DMRGM can be overcome by hematopoietic stem cell transplantation (HSCT). For external validation, the BeatAML database was downloaded, and a significant association between DMRGM and OS was confirmed (P < 0.05). CONCLUSION: Our study provides an overview of DMRGM in AML patients, which was identified as a risk factor for poor prognosis.
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Metilación de ADN , Leucemia Mieloide Aguda , Humanos , Pronóstico , Estudios Retrospectivos , Isocitrato Deshidrogenasa/genética , Nucleofosmina , Mutación , Leucemia Mieloide Aguda/genética , Metilasas de Modificación del ADN/genética , Genes ReguladoresRESUMEN
The NLR family CARD domain containing 3 (NLRC3) gene has been reported to have a crucial effect on immunity, inflammation, and tumorigenesis. However, the clinical relevance of NLRC3 in lung adenocarcinoma (LUAD) remains unclear. This study analyzed both RNA sequencing data and corresponding clinical outcomes obtained from public databases to identify (i) NLRC3 as a tumor suppressor in LUAD and (ii) its predictive value for the likelihood of patient responsiveness to immunotherapy. The results showed that NLRC3 expression was reduced in LUAD and was lower in advanced-stage tumors. Additionally, reduced NLRC3 expression was correlated with worse patient prognosis. The protein level of NLRC3 was also observed to have prognostic significance. Moreover, downregulation of NLRC3 was found to suppress the chemotaxis and infiltration of antitumor lymphocyte subpopulations as well as natural killer cells. Mechanistic analysis indicated that NLRC3 may be involved in immune infiltration by regulating chemokines and their receptors in LUAD. Furthermore, NLRC3 functions as a molecular switch in macrophages, whereby it mediates the polarization of M1 macrophages. Patients with high NLRC3 expression were also found to exhibit a more promising response to immunotherapy. In conclusion, NLRC3 could serve as a potential prognostic biomarker for LUAD, help predict the immunotherapeutic response of patients, and guide personalized strategies for the treatment of LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Pronóstico , Quimiotaxis , Biomarcadores , Péptidos y Proteínas de Señalización IntercelularRESUMEN
INTRODUCTION: Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe hematopoietic stem cell transplantation complication with high mortality and a poor patient prognosis. The pathogenesis of TA-TMA is not yet clear. In previous studies, the conclusions of different centers remain controversial. We conducted a systematic review and meta-analysis of nine selected risk factors that might be associated with the onset of TA-TMA. MATERIALS AND METHODS: PubMed databases were searched from their inception up to 15 September 2021, for relevant studies. The articles included unprocessed data related to one or more of the risk factors discussed in this meta-analysis, including recipient gender, donor type, graft source, pretreatment, infection, aGVHD, diagnosis, total body irradiation (TBI), and CMV infection. The outcome is the incidence rate (IR) of TA-TMA. RESULTS AND CONCLUSIONS: According to the sixteen articles included, risk factors included in this Meta-analysis included gender, unrelated donor source (95% CI: 1.29-2.01), graft source from peripheral blood stem cell (PBSC)(95% CI: 0.48-0.97), RIC/NMA, class II-IV aGVHD (95% CI: 2.22-4.78), nonmalignant disease, TBI. However, inconsistent diagnostic criteria for TA-TMA and the limited number of studies have an impact on the results of the study. More prospective cohort studies and More accurate diagnostic criteria are needed.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Microangiopatías Trombóticas , Humanos , Estudios Prospectivos , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/epidemiología , Microangiopatías Trombóticas/etiología , Factores de Riesgo , Incidencia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) is a fatal post-transplant complication. It has a high mortality rate and worse prognosis, but treatment strategies remain controversial. We screened 6 out of 3453 studies on the treatment of TA-TMA. These investigations compared 5 treatment strategies with a network meta-analysis approach. The final outcome was the proportion of patients who responded to these therapies. There were significant differences in response rates for each treatment. Achieving analysis through direct and indirect evidence in the rank probabilities shows that rTM (recombinant human soluble thrombomodulin) is most likely to be rank 1 (64.98%), Eculizumab intervention rank 2 (48.66%), ISM (immunosuppression manipulation) rank 3 (32.24%), TPE (therapeutic plasma exchange) intervention rank 4 (69.56%), and supportive care intervention rank 5 (70.20%). Eculizumab and ISM have significantly higher efficacy than supportive care (odds ratio (OR): 18.04, 18.21 respectively); and TPE having lower efficacy than all other TA-TMA therapies exception to supportive care. In our study, rTM and Eculizumab may be the best choice when treating TA-TMA.
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Trasplante de Células Madre Hematopoyéticas , Microangiopatías Trombóticas , Humanos , Metaanálisis en Red , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Pronóstico , Intercambio Plasmático , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/terapiaRESUMEN
Background: Arthroscopic microfracture for osteochondral lesion of the talus (OLT) has shown good functional outcomes in the short and long term. Purpose: To investigate 5-year radiographic and clinical outcomes after arthroscopic microfracture in treatment of OLT and the effectiveness of adjunct therapies including platelet-rich plasma (PRP) and hyaluronic acid (HA). Study Design: Cohort study; Level of evidence, 2. Methods: We prospectively enrolled 432 patients who underwent arthroscopic microfracture for OLT from May 1, 2011, to May 31, 2015. Magnetic resonance imaging (MRI) and weightbearing radiographs were performed annually after the initial surgery. The MOCART (magnetic resonance observation of cartilage repair tissue) score was used to evaluate the structure of the repaired cartilage on MRI, and patient-reported outcomes (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale [AOFAS] and the Foot and Ankle Outcome Score) were collected annually. The primary outcome measure was 5-year AOFAS score. We recorded baseline characteristics including age, body mass index (BMI), and lesion size, and other potentially related factors including number of PRP/HA injection and change in BMI from baseline. Results: Included were 355 patients, all with minimum 5-year follow-up data. The overall reoperation rate was 9.0% (32 of 355). According to multivariable analysis, 5-year AOFAS scores were associated with number of PRP injections (correlation coefficient, 3.12 [95% CI, 2.36 to 3.89]; P < .001), BMI at baseline (correlation coefficient, -0.222 [95% CI, -0.363 to -0.082]; P = .002), and mean BMI change from baseline (correlation coefficient, -1.15 [95% CI, -1.32 to -0.98]; P < .001). When comparing number of PRP injections (0, 1-2, or ≥3), we found that patients who had serial PRP injection (≥3 with at least a 3-month interval between injections) had diminished functional and radiographic deterioration over time. Conclusion: Arthroscopic microfracture improved patient-reported and structural outcomes for patients with OLT at 5 years after surgery. Serial PRP injections and reduction in BMI from baseline were able to slow radiographic and functional deterioration. Future trials regarding the combination of microfracture and PRP in treatment of OLT should focus on the efficacy of longer term, intra-articular, serial injections of PRP instead of single injections.
RESUMEN
Acute myeloid leukemia (AML) is a complex, heterogeneous malignant hematologic disease. Although multiple prognostic-related genes gave been explored in previous studies, there are still many genes whose prognostic value remains unclear. In this study, a total of 1532 AML patients from three GEO databases were included, five genes with potential prognostic value (DLC1, NF1B, DENND5B, TANC2 and ELAVL4) were screened by weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE). Based on this, we conducted survival analysis of the above five genes through the TCGA database and found that low level of DLC1 was detrimental to the long-term prognosis of AML patients. We also performed external validation in 48 AML patients from our medical center to analyze the impact of DLC1 level on prognosis. In conclusion, DLC1 may be a potential marker affecting the prognosis of AML, and its deficiency is associated with poor prognosis.
RESUMEN
BACKGROUND AND OBJECTIVES: Platelets are affected by many factors, such as infectious or aseptic inflammation, and different inflammatory states may induce either thrombocytopenia or thrombocytosis. Tumor necrosis factor α (TNFα) is an important inflammatory cytokine that has been shown to affect the activity of hematopoietic stem cells. However, its role in megakaryocyte (MK) development and platelet production remains largely unknown. This study aimed to investigate the effects of TNFα on MK and platelet generation. METHODS AND RESULTS: The ex vivo study with human CD34+ cells demonstrated that TNFα differentially modulated commitment toward the MK lineage. Specifically, a low concentration of 0.5 ng/ml TNFα promoted MK maturation, proplatelet formation, and platelet production, whereas a high concentration of 10 ng/ml or more TNFα exhibited a substantial inhibitory effect on MK and platelet production. The distinct effect of TNFα on MKs was mainly dependent on TNFα receptor 1. TNFα differentially regulated the MAPK-ERK1/2 signaling pathway and the cytoskeletal proteins cofilin and MLC2. The in vivo study with Balb/c mice indicated that low-dose or high-dose TNFα administration differentially affected short-term platelet recovery after bone marrow transplantation. CONCLUSIONS: Our study revealed distinct roles for TNFα in megakaryopoiesis and thrombopoiesis and may provide new insights regarding the treatment for platelet disorders.