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1.
Environ Pollut ; 357: 124409, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38908676

RESUMEN

When Cr(VI) and Cr(III) coexist, the reasonable assessment of the combined toxicity of chromium in soil and its ecological risk is still not well resolved. In the present study, exogenous mixed concentration combinations were set up to determine the interaction and combined toxicity of Cr(VI) and Cr(III), which were quantified as measured total and resin extractable forms for dose-response experiments with barley root elongation. The concept of toxicity equivalence "α" (the ratio of toxicity intensity coefficient between Cr(VI) and Cr(III), which can be expressed as the relative toxic strength of Cr(VI) to Cr(III)) was proposed for the toxicity assessment of mixed-valence chromium in soil. The results showed that the dose-response relationship was determined more precisely by the extended independent action model (e-IA) than traditional models (e.g., concentration addition model), and the mutual antagonism for resin extractable form (Resin-Cr) was stronger than the measured total form (T-Cr). The values of toxicity equivalence (α) between coexisting Cr(VI) and Cr(III) as Resin-Cr and T-Cr were 0.74 and 160, respectively, which indicated Resin-Cr(III) had relatively stronger toxicity than Resin-Cr(VI), while T-Cr(III) was much less than T-Cr(VI). The α values between Cr(VI) and Cr(III) decreased with their more active forms (decreased to about 0.5% of the original), even as total concentration and activity in solutions, making a dialectical view of the toxicity of both in different forms necessary. Finally, the log-logistic models were developed, enabling mixed-valence Cr toxicity to be assessed from a unilateral perspective using the Cr(III) equivalence concentration (Cr(III)-eq). This work provided innovative ideas for ecological threshold studies for mixed-valence metals in soils.

2.
Org Lett ; 26(12): 2381-2386, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38488149

RESUMEN

Organic sulfones are an important class of chemical compounds widely used in many research fields. The direct decarboxylative sulfonylation of carboxylic acids is attractive but challenging, particularly when iron is used as a metal catalyst. Herein, we describe a photoinduced iron-catalytic method for the synthesis of sulfones directly using carboxylic acids via a radical-based decarboxylation. This protocol is mild, highly efficient, and easy-to-operate. A broad scope of carboxylic acids and carbon electrophiles could be well tolerated. A mechanism involving the iron-catalyzed decarboxylation, radical transfer, single-electron reduction, and nucleophilic attack is proposed.

3.
Org Lett ; 26(10): 2029-2033, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38437519

RESUMEN

Herein, we report an efficient photoinduced iron-catalyzed strategy for cross-couplings of alkyl carboxylic and acrylic acids, which provides a powerful tool for the synthesis of a variety of alkenes with polar functional groups. This novel synthetic methodology can also be applied to the preparation of ketones by using α-keto acids. Mechanistic experiments revealed preliminary mechanistic details. Diverse functionalization could be achieved, which may help streamline the synthesis of complex analogues for drug discovery.

4.
J Periodontal Res ; 59(1): 151-161, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37882070

RESUMEN

BACKGROUND AND OBJECTIVE: Haploinsufficiency of Runx2 (Runx2+/- ) causes dental anomalies. However, little is known about the involvement of Runx2 in the maintenance of dentin, cementum, and the periodontal ligament (PDL) during adulthood. This study aimed to observe the effects of Runx2+/- on homeostasis of the periodontal complex. MATERIALS AND METHODS: A total of 14 three-month-old Runx2+/- mice and their wild-type littermates were examined using micro-computed tomography, histology, and immunohistochemistry. Phenotypic alterations in the dentin, cementum, and PDL were characterized and quantified. RESULTS: Haploinsufficiency of Runx2 caused cellular changes in the PDL space including reduction of cell proliferation and apoptosis, and irregular attachment of the collagen fibers in the PDL space into the cementum. Absence of continuous thickness of cementum was also observed in Runx2+/- mice. CONCLUSION: Runx2 is critical for cementum integrity and attachment of periodontal fibers. Because of its importance to cementum homeostasis, Runx2 is essential for homeostasis of periodontal complex.


Asunto(s)
Cemento Dental , Ligamento Periodontal , Ratones , Animales , Microtomografía por Rayos X , Inmunohistoquímica , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética
5.
J Craniofac Surg ; 34(8): e743-e749, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37463306

RESUMEN

OBJECTIVE: Counterclockwise rotation of mandible can cause condylar resorption and condylar displacement posteroinferiorly after maxillary orthognathic surgery with mandibular in patients with high-angle mandibular retrognathism. This study was aimed to evaluate long-term stability >2 years and postoperative changes of condylar displacement. MATERIALS AND METHODS: In 15 patients who underwent Le Fort I osteotomy with mandibular autorotation, postoperative stability was cephalometrically investigated until 2 years. Condylar changes were analyzed with transcranial temporomandibular joint projection. Correlation between condylar displacement and surgical movement was analyzed. RESULTS: Significant clockwise relapse of mandible ( P <0.01 for SNB reduction and backward movement of point B) was observed between 6 months and >2 years after surgery, even though the values were small (0.5±0.1 degrees and 1.14±0.13 mm, respectively). The condyle was displaced posteroinferiorly immediately after surgery; however, it achieved a stable position at postoperative 6 weeks. The amount of vertical condylar displacement was significantly correlated with surgical change in mandibular posterior border sagittal angle, palatal plane angle, facial height ratio, and point B in the horizontal dimension. Greater mandibular rotation prompted more vertical condylar displacement. CONCLUSIONS: Small mandibular relapse in long term should be considered after maxillary orthognathic surgery with mandibular autorotation, although it is regarded as a surgical maneuver to minimize mandibular instability in patients susceptible to postoperative condylar resorption.


Asunto(s)
Cirugía Ortognática , Humanos , Osteotomía Le Fort/métodos , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Maxilar/diagnóstico por imagen , Maxilar/cirugía , Recurrencia , Cóndilo Mandibular/diagnóstico por imagen , Cóndilo Mandibular/cirugía , Cefalometría/métodos
6.
Diabetes Metab Syndr Obes ; 15: 3739-3751, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36474726

RESUMEN

Purpose: As a formula of traditional Chinese medicine (TCM), Huoxue Jiangtang Decoction (HJD) has positive effects on diabetes mellitus (DM) through improving of the metabolism of glycolipid and the function of ß-cell. Hence, this research aims to explore the potential therapeutic effects of HJD on diabetes and reveal its underlying mechanisms. Methods: Diabetic rat models induced by high-fat diet (HFD) and streptozotocin (STZ) were included in this study. Following successful modeling, diabetic rats were treated with HJD, and then its therapeutic effects in eight weeks were evaluated. In addition to biochemical indicators, two-bottle preference tests were carried out to examine the rats' preferences for fat and sugar, and 16S rRNA gene sequencing was performed to disclose the differences of oral microbiota among groups. Finally, Pearson correlation coefficient was used to explore the correlation between oral microbiota and the preferences for fat and sugar. Results: It was found that HJD significantly improved the levels of fasting blood glucose (FBG), glucose tolerance, and dyslipidemia. Additionally, HJD contributed to decreasing preferences for fat and sugar in diabetic rats, which plays an important role in food intake. Furthermore, HJD regulated the abundance, distribution, and structure of oral microbiota in diabetic rats, serving as one of the underlying mechanisms of its antidiabetic effects. Conclusion: Taken with other formulas, HJD functions to improve the metabolism of glycolipid and the function of ß-cell by inhibiting preferences for fat and sugar, as well as regulating the oral microbiota of diabetic rats. Furthermore, a potential correlation between the oral micro-environment and preferences for fat and sugar in STZ-induced diabetic rats is likely to exist.

7.
Org Lett ; 24(26): 4766-4771, 2022 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-35758649

RESUMEN

Amide synthesis is one of the most important transformations in organic chemistry due to the broad application in pharmaceutical drugs and organic materials. In this report, we describe a mild protocol for amide formation using the readily available nitroarenes as nitrogen sources and an inexpensive iron complex as a catalyst. Because of the use of the pH-neutral conditions and the avoidance of the strong oxidant or reductant, a wide range of aromatic and aliphatic aldehydes as well as nitroarenes with various functional groups could be tolerated well. A plausible mechanism is proposed based on the detailed studies, in which iron catalyst initiates the radical process and the solvent plays a key role as O-atom acceptor.

8.
Org Lett ; 23(22): 8968-8972, 2021 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-34714097

RESUMEN

We report a general photocatalytic protocol for the remote C(sp3)-H bond amination of free aliphatic alcohols. The electron transfer between the abundant and inexpensive catalyst FeCl3 and simple alkanols under blue LED irradiation enables the alkoxy radical formation under mild redox-neutral conditions, with no need for additional oxidant and prefunctionalization. The subsequent selective 1,5-hydrogen atom transfer (HAT) and amination provide a simple and efficient way to access molecular complexity from readily available and bulk alcohols.

9.
Org Biomol Chem ; 19(28): 6346-6352, 2021 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-34231622

RESUMEN

An efficient indium-mediated cascade annulation reaction of 2-azidoaryl aldehydes with propargyl bromides is reported. The aromatic 5/6/6-fused heterocycles, [1,2,3]triazolo[1,5-a]quinoline derivatives, could be constructed in one pot in moderate yields with a broad substrate scope. Mechanistic studies indicated that the reaction proceeded through allenol formation, azide-allene [3 + 2] cycloaddition, and dehydration. The synthetic potential of the products including the denitrogenative functionalization and the Pd-catalyzed coupling reactions has also been explored.

10.
Front Neurorobot ; 15: 642733, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33732132

RESUMEN

This article aims to improve the problem of slow convergence speed, poor global search ability, and unknown time-varying dynamic obstacles in the path planning of ant colony optimization in dynamic environment. An improved ant colony optimization algorithm using time taboo strategy is proposed, namely, time taboo ant colony optimization (TTACO), which uses adaptive initial pheromone distribution, rollback strategy, and pheromone preferential limited update to improve the algorithm's convergence speed and global search ability. For the poor global search ability of the algorithm and the unknown time-varying problem of dynamic obstacles in a dynamic environment, a time taboo strategy is first proposed, based on which a three-step arbitration method is put forward to improve its weakness in global search. For the unknown time-varying dynamic obstacles, an occupancy grid prediction model is proposed based on the time taboo strategy to solve the problem of dynamic obstacle avoidance. In order to improve the algorithm's calculation speed when avoiding obstacles, an ant colony information inheritance mechanism is established. Finally, the algorithm is used to conduct dynamic simulation experiments in a simulated factory environment and is compared with other similar algorithms. The experimental results show that the TTACO can obtain a better path and accelerate the convergence speed of the algorithm in a static environment and can successfully avoid dynamic obstacles in a dynamic environment.

11.
Org Lett ; 23(8): 2915-2920, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33769053

RESUMEN

The selective α-C-C bond cleavage of unfunctionalized secondary (2°) and tertiary alcohols (3°) is essential for valorization of macromolecules and biopolymers. We developed a blue-light-driven iron catalysis for aerobic oxidation of 2° and 3° alcohols to acids via α-C-C bond cleavages at room temperature. The first example of oxygenation of the simple tertiary alcohols was reported. The iron catalyst and blue light play critical roles to enable the formation of highly reactive O radicals from alcohols and the consequent two α-C-C bond cleavages.

12.
Journal of Leukemia & Lymphoma ; (12): 730-734, 2021.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-929719

RESUMEN

Objective:To observe the clinical efficacy and safety of recombinant human granulocyte macrophage stimulating factor (rhGM-CSF) combined with R-CHOP regimen in treatment of diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 39 patients with newly diagnosed DLBCL treated with rhGM-CSF combined with R-CHOP regimen, and 39 patients with newly diagnosed DLBCL treated with R-CHOP regimen in Naval Medical University (Changhai Hospital) from February 2017 to November 2019 were retrospectively analyzed. The total response rate (ORR), remission rate (CR) rate, overall survival (OS), progression-free survival (PFS) and adverse reactions of both groups were compared.Results:In rhGM-CSF combined with R-CHOP regimen group and R-CHOP regimen group, ORR was 87.2% (34/39) and 82.1% (32/39), respectively, and the difference was statistically significant ( χ2 = 0.394, P = 0.53); CR rate was 71.8% (28/39) and 56.4% (22/39), respectively, and the difference was statistically significant ( χ2 = 2.006, P = 0.157). Until the last follow up on September 19, 2020, 32 patients survived and 7 patients died in rhGM-CSF combined with R-CHOP regimen group, of which 1 case died of bowel cancer, and the primary disease was still in CR. In the R-CHOP regimen group, 32 survived and 7 died. The 2-year OS rates of the two groups were 82.5% and 73.9%, respectively ( χ2 = 0.038, P = 0.845); the 2-year PFS rates of the two groups were 67.1% and 55.2%, respectively ( χ2 = 0.457, P = 0.499). Subgroup analysis results showed that there were no statistically significant differences in CR rates among germinal center B-cell (GCB) and non-GCB subgroups, Lugano stage Ⅰ-Ⅱ and Lugano stage Ⅲ-Ⅳ subgroups, aged <60 years and aged ≥60 years subgroups in rhGM-CSF combined with R-CHOP regimen group and R-CHOP regimen group (all P > 0.05). The major adverse reactions included bone marrow suppression and its inducible infections. There were no significant differences in the incidence of grade 3-4 hematological adverse reactions and infections between the two groups (all P > 0.05). All patients safely went through bone marrow suppression after support treatments without treatment-related deaths. Conclusions:rhGM-CSF combined with R-CHOP regimen is safe and effective in treatment of newly diagnosed DLBCL.

13.
Chinese Journal of Hematology ; (12): 16-22, 2020.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-799072

RESUMEN

Objective@#To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR1) and negative minimal residual disease (MRD-) .@*Methods@#A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR1/MRD- from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy.@*Results@#A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR1/MRD- was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes.@*Conclusion@#Allo-HSCT for candidate patients without further consolidation when CR1/MRD- was attained was feasible.

14.
Chinese Journal of Hematology ; (12): 16-22, 2020.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1012133

RESUMEN

Objective: To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR(1)) and negative minimal residual disease (MRD(-)) . Methods: A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR(1)/MRD(-) from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy. Results: A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR(1)/MRD(-) was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes. Conclusion: Allo-HSCT for candidate patients without further consolidation when CR(1)/MRD(-) was attained was feasible.


Asunto(s)
Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Adulto Joven , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Neoplasia Residual , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo
16.
Sci Total Environ ; 682: 591-600, 2019 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-31128372

RESUMEN

Graphene materials are high-performance adsorbents for water and soil remediation, whose oxygen containing groups bind to metal ions intensely. In this study, we prepared carboxylated graphene oxide (GO-OCH2COOH) sponge and investigated the adsorption behaviors of Cu2+ on it by both experimental and computational approaches. Carboxylation largely improved the adsorption capacity from 23.8mg/g for graphene oxide (GO) sponge to 93.8mg/g for GO-OCH2COOH. The efficient adsorption was due to the strong interaction between Cu2+ and carboxyl groups (especially in -OCH2COOH form) according to the density functional theory calculation, while epoxy and hydroxyl groups contributed lowly. The fast adsorption process was achieved within 30min, corresponding to a large k2 value of pseudo-second order model (0.061mg/g/min). The adsorption was spontaneous and exothermic according to thermodynamics analyses. The binding strength of Cu2+ on GO-OCH2COOH was so strong that pH and ionic strength had mild impact. The strong binding sites were not recyclable, but the weaker ones (more than 40%) could be regenerated by simple washing. Our results highlighted the importance of chemical design in graphene adsorbents and the potential of GO-OCH2COOH in heavy metal fixation from water and soil.

17.
Chinese Journal of Hematology ; (12): 625-632, 2019.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-805794

RESUMEN

Objective@#To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) .@*Methods@#In this study we retrospectively analyzed 158 Ph+ ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy.@*Results@#Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ2=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ2=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ2=7.908, P=0.005) .@*Conclusions@#Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph+ ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.

18.
Chinese Journal of Hematology ; (12): 990-995, 2019.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-800484

RESUMEN

Objective@#To investigate the relationship between donor chimerism and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#The clinical data of 105 patients with acute myeloid leukemia (AML) who underwent allo-HSCT and recurrence-free survival>90 days from January 2010 to January 2019 were retrospectively analyzed. The bone marrow samples were collected at 15, 30, 60, 90, 180, 270, 360 days after transplantation. Donor chimerism was detected by single nucleotide polymorphism (SNP) -PCR.@*Results@#Of the 105 patients, 43 cases were male and 62 cases were female, with a median age of 38 (16-60) years. Till April 2019, the median follow-up was 843 (94-3 261) days. Ninety days after transplantation, 18 cases relapsed, 33 cases died, and 72 cases survived. The 3-year overall survival (OS) rate was (66.8±5.1) %, and the recurrence-free survival (RFS) rate was (65.1±5.0) %. Pre-transplant disease status, pre-transplant minimal residual disease (MRD) , and 90 day post-transplantation chimerism were independent risk factors related to RFS. The risk of recurrence was significantly increased in patients with a donor chimerism rate ≤97.24% at 90 days after transplantation[HR=6.921 (95%CI 2.669-17.950) , P<0.001], which was considered as a sign of early relapse.@*Conclusion@#SNP-PCR is an applicable method for detecting donor chimerism in patients after allo-HSCT. Chimerism rate equal or less than 97.24% at 90 days after transplantation predicts a higher risk of relapse.

19.
Chinese Journal of Hematology ; (12): 990-995, 2019.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1012113

RESUMEN

Objective: To investigate the relationship between donor chimerism and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The clinical data of 105 patients with acute myeloid leukemia (AML) who underwent allo-HSCT and recurrence-free survival>90 days from January 2010 to January 2019 were retrospectively analyzed. The bone marrow samples were collected at 15, 30, 60, 90, 180, 270, 360 days after transplantation. Donor chimerism was detected by single nucleotide polymorphism (SNP) -PCR. Results: Of the 105 patients, 43 cases were male and 62 cases were female, with a median age of 38 (16-60) years. Till April 2019, the median follow-up was 843 (94-3 261) days. Ninety days after transplantation, 18 cases relapsed, 33 cases died, and 72 cases survived. The 3-year overall survival (OS) rate was (66.8±5.1) %, and the recurrence-free survival (RFS) rate was (65.1±5.0) %. Pre-transplant disease status, pre-transplant minimal residual disease (MRD) , and 90 day post-transplantation chimerism were independent risk factors related to RFS. The risk of recurrence was significantly increased in patients with a donor chimerism rate ≤97.24% at 90 days after transplantation[HR=6.921 (95%CI 2.669-17.950) , P<0.001], which was considered as a sign of early relapse. Conclusion: SNP-PCR is an applicable method for detecting donor chimerism in patients after allo-HSCT. Chimerism rate equal or less than 97.24% at 90 days after transplantation predicts a higher risk of relapse.


Asunto(s)
Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Quimerismo , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo
20.
Chinese Journal of Hematology ; (12): 932-938, 2019.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1012099

RESUMEN

Objective: To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML) . Methods: A retrospective analysis of 265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from January 2010 to January 2019 was performed. Mutation analysis was carried out by targeted sequencing technology including 200 hematological malignancy related genes. The association of TP53 mutation with clinical features was analyzed. Results: Alterations in TP53 were found in 20 (7.5%) patients, including 17 case (6.4%) of missense mutations, 2 cases (0.7%) of frame-shift deletion mutations and 1 case (0.4%) of splicing sites mutation. A total of 23 kinds of TP53 mutations were detected, most of them (16, 69.6%) were located in the DNA binding domain of exon 5-8, 4 in the DNA binding domain of exon 3-4, 2 in exon 10 and 1 in splice site, respectively. The median age of patients with TP53 alterations was higher than those without [52 (26-72) years old vs 45 (14-75) years old, P= 0.008]. The frequency of complex karyotypes was higher in patients with TP53 alterations than those without [45.0% (9/20) vs 6.1% (15/245) , P<0.001]. Median overall survival (OS) of patients with TP53 alterations was shorter than those without[14.1 (95%CI 6.78-21.42) months vs 31.4 (95%CI 13.20-49.59) months, P=0.029]. The OS of patients treated with "Decitabine + CAG" was superior than that of patients treated with "3 + 7" regimen [30.0 (95%CI 27.35-38.84) months vs 12.5 (95%CI 5.80-19.19) months, P=0.018]. Multivariate analysis indicated that TP53, DNMT3A and USH2A alterations, WBC ≥ 12.45×10(9)/L had negative impacts on OS. Conclusion: The frequency of TP53 mutation was 7.5% in our cohort. Most mutations were located in the DNA binding domain. TP53 alterations were strongly associated with older age, complex karyotype and shorter OS. Decitabine-based induction chemotherapy and hematopoietic stem cell transplantation may improve OS, more cases and/or multicenter randomized studies are needed for further confirmation.


Asunto(s)
Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Adulto Joven , Análisis Mutacional de ADN , Leucemia Mieloide Aguda/genética , Mutación , Pronóstico , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/genética
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