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Hydrides are promising candidates for achieving room-temperature superconductivity, but a formidable challenge remains in reducing the stabilization pressure below a megabar. In this study, we successfully synthesized a ternary lanthanum borohydride by introducing the nonmetallic element B into the La-H system, forming robust B-H covalent bonds that lower the pressure required to stabilize the superconducting phase. Electrical transport measurements confirm the presence of superconductivity with a critical temperature (Tc) of up to 106 K at 90 GPa, as evidenced by zero resistance and Tc shift under an external magnetic field. X-ray diffraction and transport measurements identify the superconducting compound as LaB2H8, a nonclathrate hydride, whose crystal structure remains stable at pressures as low as â¼ half megabar (59 GPa). Stabilizing superconductive stoichiometric LaB2H8 in a submegabar pressure regime marks a substantial advancement in the quest for high-Tc superconductivity in polynary hydrides, bringing us closer to the ambient pressure conditions.
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OPINION STATEMENT: Metformin is a first-line drug in the clinical treatment of type 2 diabetes. Its main molecular mechanism involves the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK), which regulates cell energy metabolism. Many clinical studies have shown that metformin can reduce the incidence and mortality of cancer in patients with or without diabetes. In vitro studies also confirmed that metformin can inhibit proliferation, promote apoptosis, and enhance the response of cells to chemical drugs and other anticancer effects on a variety of leukemia cells. In recent years, leukemia has become one of the most common malignant diseases. Although great progress has been made in therapeutic approaches for leukemia, novel drugs and better treatments are still needed to improve the therapeutic efficacy of these treatments. This article reviews the application status and possible mechanism of metformin in the treatment of leukemia to further understand the anticancer mechanism of metformin and expand its clinical application.
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Antineoplásicos , Diabetes Mellitus Tipo 2 , Leucemia , Metformina , Neoplasias , Humanos , Metformina/farmacología , Metformina/uso terapéutico , Proteínas Quinasas Activadas por AMP/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Leucemia/tratamiento farmacológicoRESUMEN
The prevalence of toxic element thallium (Tl) in soils is of increasing concern as a hidden hazard in agricultural systems and food chains. In the present work, pure biochar (as a comparison) and jacobsite (MnFe2O4)-biochar composite (MFBC) were evaluated for their immobilization effects in Tl-polluted agricultural soils (Tl: â¼10 mg/kg). Overall, MFBC exhibited an efficient effect on Tl immobilization, and the effect was strengthened with the increase of amendment ratio. After being amended by MFBC for 15 and 30 days, the labile fraction of Tl in soil decreased from 1.55 to 0.97 mg/kg, and from 1.51 to 0.88 mg/kg, respectively. In addition, pH (3.05) of the highly acidic soil increased to a maximum of 3.97 after the immobilization process. Since the weak acid extractable and oxidizable Tl were the preponderantly mitigated fractions and displayed a negative correlation with pH, it can be inferred that pH may serve as one of the most critical factors in regulating the Tl immobilization process in MFBC-amended acidic soils. This study indicated a great potential of jacobsite-biochar amendment in stabilization and immobilization of Tl in highly acidic and Tl-polluted agricultural soils; and it would bring considerable environmental benefit to these Tl-contaminated sites whose occurrence has significantly increased in recent decades near the pyrite or other sulfide ore mining and smelting area elsewhere.
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Contaminantes del Suelo , Talio , Talio/análisis , Suelo , Sulfuros , Contaminantes del Suelo/análisisRESUMEN
Qaidam cattle are a typical Chinese native breed inhabiting northwest China. They bear the characteristics of high cold and roughage tolerance, low-oxygen adaptability and good meat quality. To analyze the genetic diversity of Qaidam cattle, 60 samples were sequenced using whole-genome resequencing technology, along with 192 published sets of whole-genome sequencing data of Indian indicine cattle, Chinese indicine cattle, North Chinese cattle breeds, East Asian taurine cattle, Eurasian taurine cattle and European taurine cattle as controls. It was found that Qaidam cattle have rich genetic diversity in Bos taurus, but the degree of inbreeding is also high, which needs further protection. The phylogenetic analysis, principal component analysis and ancestral component analysis showed that Qaidam cattle mainly originated from East Asian taurine cattle. Qaidam cattle had a closer genetic relationship with the North Chinese cattle breeds and the least differentiation from Mongolian cattle. Annotating the selection signals obtained by composite likelihood ratio, nucleotide diversity analysis, integrated haplotype score, genetic differentiation index, genetic diversity ratio and cross-population extended haplotype homozygosity methods, several genes associated with immunity, reproduction, meat, milk, growth and adaptation showed strong selection signals. In general, this study provides genetic evidence for understanding the germplasm characteristics of Qaidam cattle. At the same time, it lays a foundation for the scientific and reasonable protection and utilization of genetic resources of Chinese local cattle breeds, which has great theoretical and practical significance.
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Variación Genética , Selección Genética , Secuenciación Completa del Genoma , Animales , Bovinos/genética , China , Secuenciación Completa del Genoma/veterinaria , Filogenia , Cruzamiento , HaplotiposRESUMEN
To evaluate the co-transplantation efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) and peripheral blood stem cells (PBSCs) as a novel approach for refractory or relapsed severe aplastic anemia (R/R SAA) in children and adolescents, thirty-two children and adolescents diagnosed with R/R SAA underwent a retrospective chart review. The patients were categorized into two groups based on the source of PBSCs: the matched sibling donor (MSD) group and the unrelated donor (UD) group. No adverse events related to UC-MSC infusion occurred in any of the patients. The median time for neutrophil engraftment was 13 days (range: 10-23 days), and for platelets, it was 15 days (range: 11-28 days). Acute GVHD of Grade I-II and moderate chronic GVHD were observed in 21.8 and 12.5% of cases, respectively. No statistically significant differences were found between the MSD and UD groups in terms of engraftment, GVHD, and complications, including infection and hemorrhagic cystitis. The median follow-up time was 38.6 months (range: 1.4-140.8 months). As of October 31, 2021, five patients had succumbed, while 27 (84.4%) survived. The 5-year OS rate showed no statistically significant difference between the MSD and UD groups (84.8 ± 10.0 vs. 82.4 ± 9.2%, p = 0.674). In conclusion, the application of UC-MSCs in the treatment of R/R SAA in PBSC transplantation is reliable and safe, they had no graft rejection, low incidence of severe GVHD which may have been contributed by the co-infusion of MSC.
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Anemia Aplásica , Trasplante de Células Madre Mesenquimatosas , Humanos , Anemia Aplásica/terapia , Anemia Aplásica/mortalidad , Niño , Adolescente , Masculino , Femenino , Preescolar , Trasplante de Células Madre Mesenquimatosas/métodos , Estudios Retrospectivos , Trasplante de Células Madre de Sangre Periférica/métodos , Recurrencia , Enfermedad Injerto contra Huésped , Lactante , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodosRESUMEN
Thallium (Tl) is a highly toxic metal, and its contamination in soils entails high risks to human health via food chain. It remains largely unknown of the effects of applying biochar on Tl uptake in paddy systems despite that few studies have shown that biochar exhibits great potential for decreasing Tl bioavailability in soils. Herein, we examined the mitigating effects of the application of biochar (5 and 20 g/kg pristine biochar; 5 and 20 g/kg Fe/Mn-modified biochar) on Tl uptake in paddy soil and rice plant after an entire rice growth period. The results suggested that the application of Fe/Mn-modified biochar (FMBC) considerably mitigated the accumulation of Tl in different tissues of rice plants. Specifically, total Tl content in rice plants treated with FMBC-20 decreased by over 75% compared with control experiment. In addition, the amendment of FMBC in Tl-rich paddy soils can enhance the communities of microorganisms (Actinobacteria and Proteobacteria). Further analysis of the soil microbial symbiosis network revealed that FMBC promotes the living microorganisms to play modular synergistic interactions, which is crucial for FMBC-induced Tl stabilization in soils. All these findings indicated that FMBC is an efficient and environmentally friendly Tl-immobilization alternative material and can be potentially used in the remediation of Tl-contaminated paddy soils and/or cropland.
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Carbón Orgánico , Oryza , Contaminantes del Suelo , Suelo , Talio , Oryza/crecimiento & desarrollo , Carbón Orgánico/química , Suelo/química , Microbiología del SueloRESUMEN
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielomonocítica Crónica , Humanos , Pronóstico , Trasplante Homólogo/efectos adversos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
Thallium (Tl) is a rare and extremely toxic metal whose toxicity is significantly higher than cadmium (Cd), lead (Pb) and antimony (Sb). The extensive utilization of Tl-bearing minerals, such as mining activities, has led to severe Tl pollution in a variety of natural settings, while little is known to date about its effect on the microbial diversity in paddy soils. Also, the geochemical behavior of Tl in the periodical alterations between dry and wet conditions of paddy soils remains largely unknown. Herein, the sequential extraction method and 16S rRNA gene sequence analysis were adopted to analyze Tl's migration and transformation behavior and the microbial diversity in the paddy soils with different pollution levels. The results indicated that Tl was mainly concentrated in reducible fraction, which is different from other types of soils, and may be closely attributed to the abundance of Fe-Mn (hydr)oxides in the paddy rhizospheric soils. Further analysis revealed that pH, total S, Pb, Sb, Tl and Cd were the dominant environmental factors, and the enrichment level of these potentially toxic metal(loid)s (PTMs) exerted obvious impacts on the diversity and abundance of microorganism in the rhizospheric soils, and regulating microbial community. The geochemical fractionation of Tl was closely correlated to soil microorganisms such as Fe reducing bacteria (Geothrix) and sulfate reducing bacteria (Anaerolinea), playing a critical role in Tl geochemical cycle through redox reaction. Hence, further study on microorganisms of paddy rhizospheric soils is of great significance to the countermeasures for remediating Tl-polluted paddy fields and protect the health of residents.
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Contaminantes del Suelo , Talio , Talio/análisis , Talio/química , Talio/toxicidad , Suelo/química , Contaminantes del Suelo/análisis , ARN Ribosómico 16S/genética , Cadmio/análisis , Plomo/análisis , SulfurosRESUMEN
Nanoplastics (NPs) has become a worrying serious environmental problem. However, the toxicological effects and mechanisms of NPs on hematopoiesis are still unknown. To this end, male C57BL/6J mice were directly exposed to the serial concentration gradient of polystyrene NPs (PSNPs, 0, 30, 60, and 120 µg d), respectively, for 42 days by intragastric administration. Results show that PSNPs were clearly visible in bone tissues, meanwhile, induced the count of major blood indicators (WBC, RBC, and LYM) decreased. H&E staining displayed that exposed to PSNPs can cause hematopoietic damage of BM and extramedullary hematopoiesis in spleen. Flow cytometry result show that the proportion of LSK represented a dose-dependent significantly decreased after PSNPs exposure. Further research found that PSNPs can cause the systemic oxidative stress occurs manifested as MDA accumulated. In addition, as the dose of PSNPs increased, the fluorescence intensity of Keap1 and p53 in femur sections gradually increased, meanwhile, the expression of cell oxeiptosis signal pathway Keap1/PGAM5/AIFM1 and the cell senescence signal pathway p53/p21 was all increased, markedly. Overall, our study demonstrated that PSNPs exposure caused oxidative stress, potentially resulting in cell oxeiptosis and senescence to develop haematotoxicity in C57BL/6J mice.
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Microplásticos , Poliestirenos , Animales , Ratones , Masculino , Poliestirenos/toxicidad , Proteína 1 Asociada A ECH Tipo Kelch , Ratones Endogámicos C57BL , Proteína p53 Supresora de Tumor , Factor 2 Relacionado con NF-E2RESUMEN
Superhard materials other than diamond and cubic boron nitride have been actively pursued in the past two decades. Cubic silicon carbide, i.e., ß-SiC, is a well-known hard material with typical hardness <30 GPa. Although nanostructuring has been proven to be effective in enhancing materials' hardness by virtue of the Hall-Petch effect, it remains a significant challenge to improve hardness of ß-SiC beyond the superhard threshold of 40 GPa. Here, the fabrication of nanocrystalline ß-SiC bulks is reported by sintering nanoparticles under high pressure and high temperature. These ß-SiC bulks are densely sintered with average grain sizes down to 10 nm depending on the sintering conditions, and the Vickers hardness increases with decreasing grain size following the Hall-Petch relation. Particularly, the bulk sintered under 25 GPa and 1400 °C shows an average grain size of 10 nm and an asymptotic Vickers hardness of 41.5 GPa. Boosting the hardness of ß-SiC over the superhard threshold signifies an important progress in superhard materials research. A broader family of superhard materials is in sight through successful implementation of nanostructuring in other hard materials such as BP.
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This study aims to explore the effect of the ITI (interferon alpha-1b, thalidomide, and interleukin-2) regimen on the AML1-ETO fusion gene in patients with t(8;21) acute myeloid leukemia (AML) who were in hematologic remission but positive for the AML1-ETO fusion gene. From September 2014 to November 2020; 20 patients with AML (15 from The Affiliated Cancer Hospital of Zhengzhou University, 4 from The First Affiliated Hospital; and College of Clinical Medicine of Henan University of Science and Technology, and 1 from Anyang District Hospital) with hematological remission but AML1-ETO fusion gene positivity were treated with different doses of the ITI regimen to monitor changes in AML1-ETO fusion gene levels. Twenty patients were treated with a routine dose of the ITI regimen, including 13 males and 7 females. The median patient age was 38 (14-70 years). The fusion gene was negative in 10 patients after 1 (0.5 ~ 8.6) month, significantly decreased in 4 patients after 2.8 (1 ~ 6) months, increased in 4 patients, and unchanged in 2 patients. The 4 patients with elevated levels of the fusion gene were treated with an increased dose of the ITI regimen, and all four patients became negative, for a total effective rate of 90%. The ITI regimen reduces AML1-ETO fusion gene levels in patients with AML who are in hematologic remission but are fusion gene-positive. Improvement was observed in patients' response to a higher dose administration, and patients tolerated the treatment well.
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Antineoplásicos/uso terapéutico , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Factores Inmunológicos/uso terapéutico , Interferón-alfa/uso terapéutico , Interleucina-2/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Proteínas de Fusión Oncogénica/genética , Proteína 1 Compañera de Translocación de RUNX1/genética , Talidomida/uso terapéutico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Fusión de Oncogenes/efectos de los fármacos , Adulto JovenRESUMEN
A 43-year-old man with a 23-year history of type II diabetes presented with uncontrolled hyperglycemia with frequent episodes of ketoacidosis. He was diagnosed with exogenous insulin antibody syndrome, and received high-dose methylprednisolone to treat insulin resistance. Ketoacidosis relapsed 2 years later, and the patient showed an incomplete response to glucocorticoids. We decided to administer therapeutic plasma exchange, which resulted in rapid lowering of the daily insulin requirement and improved glycemic control.
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Anticuerpos/química , Diabetes Mellitus Tipo 2/complicaciones , Inmunosupresores/efectos adversos , Insulina/uso terapéutico , Intercambio Plasmático/métodos , Adulto , Diabetes Mellitus Tipo 2/terapia , Humanos , Hiperglucemia/tratamiento farmacológico , Terapia de Inmunosupresión , Resistencia a la Insulina , Masculino , Plasmaféresis , Prevalencia , SíndromeRESUMEN
OBJECTIVE: To explore the clinical characteristics and prognostic values of TP53 gene variant in patients with acute leukemia(AL). METHODS: The clinical data of 44 newly diagnosed AL patients with TP53 variant detected by next generation sequencing (NGS) were analyzed retrospectively. Targeted sequencing technique containing 108 leukemia-related genes was used for variant analysis, and conventional R-banding technique was used for karyotype analysis. The clinical features, cytogenetics, gene variant, curative effect and survival of AL patients with TP53 gene variant were analyzed. RESULTS: The median age of AML patients with TP53 gene variant (46 years) was higher than that of ALL patients (17.5 years), and the median number of bone marrow blasts (40.5%) was lower than the latter (89.2%), the differences were statistically significant (P< 0.01). A total of 28 cases of abnormal karyotype were detected, of which 25 cases were complex karyotype, 16 cases were monomeric karyotype, 14 cases had -17/17p-. The detection rates of TP53 in complex karyotype, monomeric karyotype and -17/17p- were 59.5%, 38.1% and 33.3%, respectively. Subgroup analysis showed that the detection rate of TP53 gene abnormalities in AML and ALL complex karyotypes was 73.1% and 40% respectively, the difference was statistically significant. A total of 41 TP53 gene variant types were found, and the median variant frequency was 43.58%. 75.6% variant was located in the DNA binding domain. The concomitant variant genes were mainly TET2 and IKZF1. Among 18 AML and 17 ALL patients who could be evaluated the curative effect, the CR rate of one course of treatment was 22.2% and 94.12% respectively, and the difference was statistically significant. The median RFS of 4 cases of AML with CR and 16 cases of ALL with CR were 174 and 246 days respectively, the difference was statistically insignificant. The median OS of AML and ALL was 20 and 375 days respectively, the difference was statistically significant. CONCLUSION: The TP53 gene variant is associated with the complex karyotype of AML, but has no significant effect on ALL. The variant site of TP53 gene was mainly distributed in the DNA binding domain. The remission rate of AML with TP53 gene variant was lower than that of ALL. The prognosis of AL patients with TP53 gene variant is poor, so allogeneic hematopoietic stem cell transplantation should be performed as soon as possible to prolong the survival of the patients.
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Leucemia Mieloide Aguda , Proteína p53 Supresora de Tumor , Enfermedad Aguda , Humanos , Leucemia Mieloide Aguda/genética , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/genéticaRESUMEN
[This corrects the article DOI: 10.1186/s12935-019-0993-9.].
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An efficient general methodology for the synthesis of 4-quinolinyl ethers is demonstrated via a highly reactive SNAr reaction of 4-quinolinyl sulfones with a range of structurally diversified 1°, 2°, and 3° alcohols with a wide substrate scope and high yields. By adapting this methodology, a convergent synthesis of a complex target of HCV NS3/4a protease inhibitor BI 201420 was accomplished.
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Hepatitis C , Proteínas no Estructurales Virales , Antivirales , Éteres , Hepacivirus , Humanos , Inhibidores de Proteasas/farmacología , SulfonasRESUMEN
Forefoot defects caused by accidents are very common, but their reconstruction remains a substantial challenge for plastic surgeons. The purpose of this study is to determine the anatomical structure of the first metatarsal proximal perforator-based flap and to propose its clinical application. The study was divided into two parts: an anatomical study and a clinical application. Thirty preserved lower limbs injected with red latex were chosen for observation, and the following were recorded: the course and distribution of the medialis dorsalis pedis cutaneous nerve; the origin, course, branching and distribution of the first metatarsal proximal perforator; and the communication of the perforator and the dorsal medial vessels. Clinically, six cases of forefoot skin defects were reconstructed with the first metatarsal proximal perforator-based neurocutaneous vascular flap. The medialis dorsalis pedis cutaneous nerve mainly arose from the medial branch of the superficial peroneal nerve and proceeded forward for a distance of 2.5 ± 0.4 cm under the surface of the inferior extensor retinaculum; then, the nerve divided into the medial dorsal branch and the first and second dorsal metatarsal branches. The first metatarsal proximal perforator-based neurocutaneous vessels were multisegmented and multisourced, and the first branch was closely related to the operative procedure. In terms of the clinical application, all flaps of the six cases survived completely with good appearance, texture and elasticity. The first metatarsal proximal perforators present as constant. The first metatarsal proximal perforator-based neurocutaneous vascular flap may become a useful supplemental material for the reconstruction of forefoot defects. Clin. Anat., 33:653-660, 2020. © 2019 Wiley Periodicals, Inc.
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Traumatismos de los Pies/cirugía , Antepié Humano/irrigación sanguínea , Antepié Humano/inervación , Colgajo Perforante/irrigación sanguínea , Colgajo Perforante/inervación , Trasplante de Piel/métodos , Adulto , Anciano , Cadáver , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: To investigate the value of dynamic monitoring peripheral blood lymphocyte-to-monocyte (LMR) ratio in evaluating the treatment response and prognosis of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: A total of 148 patients with ENKTL were retrospectively analyzed in the Affiliated Tumor Hospital of Zhengzhou University between March 2012 and March 2018. The optimal cut-off value of LMR was determined using the receiver operating characteristic curve (ROC) method, then patients were divided into low LMR group and high LMR group. The LMR level was dynamically measured at various time points, and the relationships between LMR and therapeutic response, and survival were analyzed. RESULTS: The complete remission rate (CR) was 85.7% in patients with high LMR at diagnosis, which was remarkably higher than that of patients with low LMR at diagnosis (64.9%) (P = 0.009). The 5-year overall survival (OS) and progression-free survival (PFS) were 49.28% and 44.89% in the low LMR group, respectively; 5-year OS and PFS in the high LMR group were 84.50% and 67.12%, respectively, significantly longer (P values were < 0.001 and 0.034, respectively). The OS and PFS of patients with elevated LMR after treatment were longer than those with decreased LMR after treatment (all P values < 0.05). The LMRs at relapse were significantly lower in both high and low LMR groups than those of the last follow-up (P values were 0.001 and 0.016, respectively). Univariate and multivariate analysis demonstrated that low LMR was an independent risk factor for poor prognosis in ENKTL patients (P values were < 0.001 and 0.009, respectively). CONCLUSIONS: Lymphocyte to monocyte ratio can be used as an indicator of treatment response, prognosis and recurrence in patients with ENKTL. Low LMR before and after treatment is a poor prognostic factor.
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BACKGROUND: Glioma is one of the most common and aggressive malignant tumors of the central nervous system. METHODS: Here, we review and explore the use of long noncoding RNA (lncRNA) as a therapeutic strategy for the targeting of gliomas. RESULTS: LncRNA is a functional RNA molecule with no protein coding function and is involved in the occurrence and progression of glioma. It is reported that the activation of several signaling pathways, including the MAPK, p53, Wnt/ß-catenin, PI3K/AKT/mTOR, and epithelial mesenchymal transformation (EMT) pathways, are involved in the regulation of gliomas. In addition, microRNAs in glioma may also interact with lncRNAs and affect tumor growth and progression. CONCLUSIONS: Therefore, the exploration of lncRNA participation in signaling pathway regulatory mechanisms and the determination of the interaction between lncRNA and miRNA may help to develop new effective therapies for the treatment of glioma.
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Regulación Neoplásica de la Expresión Génica , Glioma/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , Transducción de Señal/genética , Transición Epitelial-Mesenquimal/genética , Glioma/patología , HumanosRESUMEN
BACKGROUND The aim of this study was to investigate the correlations between ADAMTSs expression and breast invasive ductal carcinoma (IDC), and to offer a theoretical basis for novel treatment methods for IDC patients. MATERIAL AND METHODS Non-proliferative catheter of breast fibroadenoma (FA) and IDC were used as the normal control and experimental group, respectively. Immunohistochemical (IHC) staining and Western blot (WB) analysis was used to assess protein expression levels of ADAMTS8, ADAMTS18, and ADAMTS20 in both FA and IDC tissues. The results of IHC, the relationship between the protein expression and the tumor molecular classification, and clinical pathological parameters were all evaluated. RESULTS IHC and WB results showed that the expression of ADAMTS8/18 in IDC samples was higher than in FA samples, while the expression of ADAMTS20 in IDC samples was lower than that in FA samples. According to the results of WB, the level of ADAMTS8 was higher in the HER2+ group than in the HER2- group and FA group. The expression of ADAMTS18 in the HR+ (including ER+ and PR+) group was significantly higher than in the HR- group and FA group. The expression of ADAMTS18 protein was also higher in the Ki67+ group than in the Ki67- group. ADAMTS20 was higher in HER2+ IDC compared with the basal subtype of IDC. CONCLUSIONS ADAMTS8/18/20 levels were not significantly correlated to the molecular subtype of IDC. ADAMTS18/20 was significantly associated with histological grade of IDC. ADAMTS8 may predict poor prognosis results of IDC patients.
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Proteínas ADAMTS/biosíntesis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Proteínas ADAMTS/genética , Adulto , Anciano , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/clasificación , Carcinoma Ductal de Mama/genética , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Receptores de Estrógenos/metabolismo , TranscriptomaRESUMEN
Previous studies have confirmed that CD133+ cells in laryngeal tumor tissue have the characteristics of cancer stem cells. Bmi-1 gene expression is central to the tumorigenicity of CD133+ cells. In this study, we tried to develop a new siRNA carrier system using chitosan-methoxypolyethylene nanoparticles (CS-mPEG-NPs) that exhibit higher tumor-targeting ability and enhanced gene silencing efficacy in CD133+ tumor stem cells. It is hoped to block the self-renewal and kill the stem cells of laryngeal carcinoma. The mPEG-CS-Bmi-1RNAi-NPs were synthesized and their characters were checked. The changes in invasion ability and sensitivity to radiotherapy and chemotherapy of CD133+Hep-2 tumor cells were observed after Bmi-1 gene silencing. The mPEG-CS-Bmi-1RNAi-NPs synthesized in this experiment have a regular spherical form, a mean size of 139.70 ±6.40 nm, an encapsulation efficiency of 85.21 ± 1.94%, with drug loading capacity of 18.47 ± 1.83%, as well as low cytotoxicity, providing good protection to the loaded gene, strong resistance to nuclease degradation and high gene transfection efficiency. After Bmi-1 gene silencing, the invasion ability of CD133+ cells was weakened. Co-cultured with paclitaxel, the survival rates of CD133+Bmi-1RNAi cells were lower. After radiotherapy, the mean growth inhibition rate of CD133+/Bmi-1RNAi cells was significantly lower than CD133+ cells. In conclusion, the mPEG-CS nano-carrier is an ideal vector in gene therapy, while silencing the Bmi-1 gene can enhance the sensitivity of CD133+ tumor stem cells to chemoradiotherapy and abate their invasion ability.