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1.
Ann Hematol ; 103(8): 3247-3250, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38888615

RESUMO

Here, we present a rare case of myeloproliferative neoplasms (MPN) with eosinophilia harboring both BCR::ABL1 and PDGFRB rearrangements, posing a classification dilemma. The patient exhibited clinical and laboratory features suggestive of chronic myeloid leukemia (CML) and myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK), highlighting the diagnostic challenges associated with overlapping phenotypes. Despite the complexity, imatinib treatment swiftly achieved deep molecular remission, underscoring the therapeutic efficacy of tyrosine kinase inhibitors in such scenarios. Furthermore, the rapid attainment of deep remission by this patient in response to imatinib closely resembles that observed in MLN-TK patients with PDGFRB rearrangements. Further research is warranted to elucidate the underlying mechanisms driving the coexistence of multiple oncogenic rearrangements in MPNs and to optimize therapeutic strategies for these complex cases.


Assuntos
Eosinofilia , Proteínas de Fusão bcr-abl , Mesilato de Imatinib , Transtornos Mieloproliferativos , Receptor beta de Fator de Crescimento Derivado de Plaquetas , Humanos , Mesilato de Imatinib/uso terapêutico , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/complicações , Eosinofilia/genética , Eosinofilia/tratamento farmacológico , Proteínas de Fusão bcr-abl/genética , Rearranjo Gênico , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Feminino
2.
Biotechnol Appl Biochem ; 68(6): 1372-1385, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33169873

RESUMO

In this study, an anticalin that could specifically bind paraquat (PQ), a quaternary nitrogen herbicide, as a new set of engineered receptor protein with antibody-like properties was generated to detect PQ concentration. To this end, a native and random library was constructed and engineered to allow in vitro transcription and translation using an Escherichia coli lysate system. Meanwhile, a PQ derivative that carries an active aliphatic carboxylate group at the end of an aliphatic spacer arm was synthesized. Then, this compound was coupled covalently to the carrier protein bovine serum albumin/ovalbumin and amino-functionalized paramagnetic beads. Alternating selection in solution and immobilization in microtiter wells were used to pan mRNA-ribosome-antibody complexes. After several rounds of ribosome display, three variants were selected from a random library of the bilin-binding protein. The variants that could bind complex PQ with high affinity and exhibit IC50 values as low as 14.039 ± 0.970 ng/mL were identified. Moreover, the limits of detection reached 0.083 ± 0.011 ng/mL. Our data suggest that the generation of anticalins may provide a promising alternative to recombinant antibody fragments to create a stable receptor protein against hapten with bioanalytical relevance.


Assuntos
Lipocalinas/química , Ovalbumina/química , Paraquat/química , Ribossomos/química , Soroalbumina Bovina/química , Animais , Bovinos , Fenômenos Magnéticos , Estrutura Molecular , Biblioteca de Peptídeos
3.
Clin Appl Thromb Hemost ; 30: 10760296241271358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39109998

RESUMO

Disseminated intravascular coagulation (DIC) poses a high mortality risk, yet its exact impact remains contentious. This study investigates DIC's association with mortality in individuals with sepsis, emphasizing multiple organ function. Using data from the Peking University People's Hospital Investigation on Sepsis-Induced Coagulopathy database, we categorized patients into DIC and non-DIC groups based on DIC scores within 24 h of ICU admission (< 5 cutoff). ICU mortality was the main outcome. Initial data comparison preceded logistic regression analysis of mortality factors post-propensity score matching (PSM). Employing mediation analysis estimated direct and indirect associations. Of 549 participants, 131 were in the DIC group, with the remaining 418 in the non-DIC group. Following baseline characteristic presentation, PSM was conducted, revealing significantly higher nonplatelet sequential organ failure assessment (nonplt-SOFA) scores (6.3 ± 2.7 vs 5.0 ± 2.5, P < 0.001) and in-hospital mortality rates (47.3% vs 29.5%, P = 0.003) in the DIC group. A significant correlation between DIC and in-hospital mortality persisted (OR 2.15, 95% CI 1.29-3.59, P = 0.003), with nonplt-SOFA scores (OR 1.16, 95% CI 1.05-1.28, P = 0.004) and hemorrhage (OR 2.33, 95% CI 1.08-5.03, P = 0.032) as predictors. The overall effect size was 0.1786 (95% CI 0.0542-0.2886), comprising a direct effect size of 0.1423 (95% CI 0.0153-0.2551) and an indirect effect size of 0.0363 (95% CI 0.0034-0.0739), with approximately 20.3% of effects mediated. These findings underscore DIC's association with increased mortality risk in patients with sepsis, urging anticoagulation focus over bleeding management, with organ dysfunction assessment recommended for anticoagulant treatment efficacy.


Assuntos
Coagulação Intravascular Disseminada , Insuficiência de Múltiplos Órgãos , Sepse , Humanos , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/mortalidade , Sepse/complicações , Sepse/mortalidade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Mortalidade Hospitalar
4.
Clin Imaging ; 83: 166-171, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35074625

RESUMO

PURPOSE: To understand the reliability of low-dose chest computed tomography (LDCT) in coronary artery calcification (CAC) assessment and evaluate the performance of different reconstruction kernels against the standard cardiac computed tomography (CaCT) as reference. MATERIALS AND METHODS: Patients from the NELCIN-B3 screening program who underwent CaCT and LDCT scans were analyzed retrospectively. LDCT were reconstructed with smooth, standard, and sharp kernels (Group B1, B2 and B3) to compare against standard CaCT (Group A). The image quality was evaluated by noise value, signal-to-noise ratio (SNR), and contrast to noise ratio (CNR); moreover, radiation dose was recorded for both scans. Coronary artery calcification scores (CACS) were measured with volume, mass and Agatston standards. Agatston score was divided into four cardiovascular risk categories (0, 1-99, 100-399, and >400). The agreement in CACS and risk classification between LDCT and CaCT was analyzed by intra-group correlation coefficient (ICC) and Kappa test. RESULTS: The sensitivity of diagnosing CAC with LDCT was 98.5% (330/335) regardless of reconstruction kernels. Group B1 demonstrated the highest agreement in raw CACS (ICC volume 0.932; mass 0.904; Agatston 0.906; all p < 0.001) and risk classification (kappa 0.757, 95% CI 0.70-0.82). Smooth-kernel reconstruction achieved lower image noise, better SNR and CNR than other kernels. The effective radiation dose in of LDCT was 41.2% lower than that of the calcium scan (p < 0.001). CONCLUSION: Reconstructing LDCT with a smooth kernel in LDCT could provide a reliable imaging method to detect and quantitatively evaluate CAC, potentially expanding the application of LDCT lung screening to incidental findings of cardiovascular disease.


Assuntos
Doença da Artéria Coronariana , Calcificação Vascular , Doença da Artéria Coronariana/diagnóstico por imagem , Humanos , Doses de Radiação , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Calcificação Vascular/diagnóstico por imagem
5.
Front Immunol ; 12: 639217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868266

RESUMO

Background: Azacitidine is commonly used in the treatment of relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the effectiveness of this monotherapy is still very low. A possible mechanism of resistance to hypomethylating agents (HMAs) is the upregulation of the expression of inhibitory checkpoint receptors and their ligands, making the combination of HMAs and immune checkpoint blockade therapy a rational approach. Although the safety of anti-programmed cell death protein (PD)-1 antibodies for patients with post-allo-HSCT remains a complicated issue, the preliminary clinical result of combining azacitidine with anti-PD-1 antibodies is encouraging; however, the safety and efficacy of this approach need further investigation. Case Presentation: We reported a case of treated secondary (ts)-AML in a patient who received tislelizumab (an anti-PD-1 antibody) in combination with azacitidine. The patient relapsed after allo-HSCT and was previously exposed to HMAs-based therapy. The patient received tislelizumab for compassionate use. After the combination treatment, the patient achieved complete remission with incomplete hematologic recovery, negative minimal residual disease (MRD) by flow cytometry (FCM), and negative Wilms' tumor protein 1 (WT1). However, the patient successively developed serious immune-related adverse events (irAEs) and graft vs. host disease (GVHD) and eventually died from complications of GVHD. Conclusion: To our knowledge, this is the first case to report the combined use of tislelizumab and azacitidine to treat relapsed AML posttransplantation. This report highlights the safety concerns of using an anti-PD-1 antibody in combination with azacitidine after allo-HSCT, especially the risk of GVHD, and provides a basis for future studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Leucemia Mieloide Aguda/terapia , Anticorpos Monoclonais Humanizados/efeitos adversos , Azacitidina/efeitos adversos , Terapia Combinada , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfoma Folicular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/etiologia , Transplante Homólogo
6.
J Appl Genet ; 50(4): 391-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19875891

RESUMO

Natural killer (NK) cells are the most abundant lymphocyte population in the decidua. These cells express killer immunoglobulin-like receptors (KIRs), which upon recognition of HLA class I molecules on trophoblasts may either stimulate NK cells (activating KIRs) or inhibit them (inhibitory KIRs) to produce soluble factors necessary for the maintenance of pregnancy. KIR genes exhibit extensive haplotype polymorphism; individuals differ in both the number and kind (activating vs. inhibitory) of KIR genes. This polymorphism affects NK cell reactivity and susceptibility to diseases, including gynecological disorders. Therefore we KIR-genotyped 149 spontaneously aborting women and 117 control multiparae (at least 2 healthy-born children). Several genotypes (i.e. combinations of various KIR genes) were differently distributed among the patients and control subjects. Differences were observed in the numbers and the ratios of activating to inhibitory KIRs between patients and healthy women: (i) genotypes containing 6 activating KIR genes were less frequent and those containing 6 inhibitory KIR genes were more frequent in patients than in control subjects, and (ii) an excess of inhibitory KIRs (activating-to-inhibitory KIR gene ratios of 0.33 to 0.83) was associated with miscarriage, whereas ratios close to equilibrium (0.86-1.25) seemed to be protective. In addition, the results suggest for the first time that sporadic and recurrent spontaneous abortions as well as miscarriage in the presence or absence of autoantibodies may have different KIR genotypic backgrounds.


Assuntos
Aborto Espontâneo/genética , Aborto Espontâneo/imunologia , Receptores KIR/genética , Aborto Habitual/genética , Aborto Habitual/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Polônia , Gravidez , Adulto Jovem
7.
Artigo em Chinês | WPRIM | ID: wpr-1017267

RESUMO

Objective:To compare the trueness of incisal guidance of implant-supported single crowns designed by patient-specific motion(PSM)with that designed by average-value virtual articulator(AVA).Methods:The study had recruited 12 participants with complete dentition and stable incisal guidance.An intraoral scanner was used to scan digital casts and record two types of patient-specific mo-tion(data only including protrusive movement,and data including protrusive movement and lateral pro-trusive movement).The lingual surfaces of the maxillary incisors which guided the protrusive movement was selected and elevated to create a reference cast.A maxillary central incisor of original casts was vir-tually extracted and implanted to generate a working cast.The Dental system software program was used to design implant-supported single crowns with the anatomical coping design method.The incisal guidance was designed by different methods.The incisal guidance in control group was designed by the average-value virtual articulator.The incisal guidance in experiment groups was designed by the patient-specific motion only including protrusive movement(PSM1)and with the patient-specific motion including protru-sive movement and lateral protrusive movement(PSM2).The incisal guidance of prosthesis designed by these 3 methods were compared with the original incisal guidance in Geomagic Control 2015(3DSystem,America).The measurements included:Average of positive values,ratio of positive area and maximum value reflecting supra-occlusion;average of negative values,ratio of negative area and minimum value re-flecting over-correction;and root mean square reflecting overall deviation.Results:Statistical data were collected using the median(interquartile range)method.The average of positive values,ratio of positive area and average of negative values of the PSM2 group were smaller than those of the control group[8.0(18.8)μm vs.37.5(47.5)μm;0vs.7.2%(38.1%);-109.0(63.8)μm vs.-66.5(64.5)μm],and the ratio of negative area of PSM2 group was larger than those of the control group[52.9%(47.8%)vs.17.3%(45.3%)],with significant differences(P all<0.05).The ratio of positive area[0.1%(7.0%)]and average of negative values[-97.0(61.5)μm]of PSM1 group,were smaller than those of the control group,and the ratio of negative area[40.7%(39.2%)]of the PSM1 group was larger than that of the control group,with significant differences(P<0.05).The average of positive values[20.0(42.0)μm]and ratio of positive area of PSM1 group was larger than that of the PSM2 group with significant differences(P<0.05).Conclusion:To establish the incisor guidance of implant-supported single crowns,compared with the average-value virtual articulator and the patient-specific motion only including protrusive movement,the patient-specific motion including protrusive movement and lateral protrusive movement is more conducive to reducing the protrusive interference of prosthesis and improving the occlusal fit.

8.
Front Oncol ; 9: 1358, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850234

RESUMO

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following chemotherapy is part of standard treatment protocol for patients with acute myeloid leukemia (AML). FUS-ERG+ AML is rare but has an extremely poor prognosis even with allo-HSCT in remission, possibly due to its a leukemia stem cell (LSC)-driven disease resulting in chemotherapy resistance and a novel therapy is urgently required. It has been reported that FUS-ERG-positive AML expresses CD123, a marker of LSC, in some cases. CD123-targeted CAR T cell (CART123) is promising immunotherapy, but how to improve the complete remission (CR) rate and rescue potential hematopoietic toxicity still need to explore. Case Presentation: We used donor-derived CART123 as part of conditioning regimen for haploidentical HSCT (haplo-HSCT) in a patient with FUS-ERG+ AML who relapsed after allogeneic transplantation within 3 months, resists to multi-agent chemotherapy and donor lymphocyte infusion (DLI) and remained non-remission, aiming to reduce these chemotherapy-resistant blasts and rescue potential hematopoietic toxicity. The blasts in BM were reduced within 2 weeks and coincided with CAR copies expansion after CART123 infusion. The patient achieved full donor chimerism, CR with incomplete blood count recovery, and myeloid implantation. Conclusion: Our results hints that CART123 reduces the chemotherapy-resistant AML blasts for FUS-ERG+ AML without affecting the full donor chimerism and myeloid implantation.

9.
Artigo em Inglês | WPRIM | ID: wpr-971591

RESUMO

Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.


Assuntos
Humanos , Regulação da Expressão Gênica no Desenvolvimento , Odontogênese , Transdução de Sinais , Dente/metabolismo
10.
Artigo em Chinês | WPRIM | ID: wpr-986043

RESUMO

Objective: To explore the current situation of work stress among nursing staff in Tianjin City and analyze its influencing factors. Methods: From August to October 2020, 26002 nursing staff from tertiary hospitals, secondary public hospitals, secondary private hospitals, primary hospitals, and other medical institutions in Tianjin City were selected as objects, and their general situation and working stress situation were surveyed by the general information questionnaire and the Nurse's Work Stressor Scale. Single factor analysis and multiple linear regression analysis were used to explore the influencing factors of work stress among nursing staff. Results: The average age of 26002 nursing staff was (33.86±8.28) years old, and the average working years were (11.84±9.12) years. There were 24874 women (95.66%) and 1128 men (4.34%). The total score of work stress was (79.82±21.69), and the average score of workload and time allocation dimension was the highest (2.55±0.79). The results of multiple linear regression analysis showed that marital status (β=-0.015, P=0.014), employment form as contract system (β=0.022, P=0.001), post as clinical nursing (β=0.048, P<0.001), education level (β=0.024, P<0.001), age (β=0.050, P<0.001), working years (β=0.075, P<0.001), and professional title (β=0.036, P<0.001) were the influencing factors of work stress, which explained 22.8% of the total variation in work stress of nursing staff (F=24.25, P<0.001) . Conclusion: The work stress among nursing staff in Tianjin City is high, the corresponding departments and nursing managers should adopt scientific management methods to reduce the workload of nursing staff according to the influencing factors of work stress, so as to create a good atmosphere for further promoting the healthy development of nursing career and nursing industry in the new era.


Assuntos
Masculino , Humanos , Feminino , Adulto , Estresse Ocupacional/epidemiologia , Recursos Humanos de Enfermagem , Centros de Atenção Terciária , Inquéritos e Questionários , Emprego
11.
Artigo em Chinês | WPRIM | ID: wpr-993118

RESUMO

Objective:To investigate the clinical effect and safety of camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma (NPC).Methods:A total of 24 patients with stage Ⅲ-IV A NPC were recruited prospectively to receive two cycles of camrelizumab combined with induction chemotherapy (docetaxel 75 mg/m 2+ cisplatin 25 mg/m 2 for three consecutive days) followed by concurrent chemoradiotherapy (prescription doses: 6 996 cGy in 33 fractions for PGTV and PGTV nd, 6 006 cGy in 33 fractions for PTV 1, 5 096 cGy in 28 fractions for PTV 2, and concurrent cisplatin chemotherapy with a dose of 75 mg/m 2). The short-term efficacy and adverse reactions were evaluated. Results:After induction therapy, nasopharyngeal lesions showed an objective response rate (ORR) of 91.6%, including 45.8% of complete response (CR) and 45.8% of partial response (PR); cervical lymph nodes showed an ORR of 95.8% (CR: 4.2%; PR: 91.6%). Seventeen patients accepted a reexamination under a nasopharyngoscope, and the biting biopsy result indicated that 13 patients among them had complete pathologic response. After concurrent chemoradiotherapy, nasopharyngeal lesions and cervical lymph nodes showed CR rates of 83.3% and 91.7% and PR rates of 16.7% and 8.3%, respectively. After the induction therapy, 13 patients with stage IV A NPC had ORR (PR) rates of 92.4% and 92.4%, respectively, at nasopharyngeal lesions and cervical lymph nodes. After concurrent chemoradiotherapy, the patients with stage IV A NPC had CR rates of 84.6% and 92.3% and PR rates of 15.4% and 7.7%, respectively, at nasopharyngeal lesions and cervical lymph nodes. Major adverse reactions include leukopenia, granulopenia, anemia, radioactive acute oropharyngeal mucositis and dermatitis, digestive tract reaction, fatigue, hypothyroidism, aminotransferase elevation, and reactive capillary hyperplasia. Conclusions:Camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy can achieve high short-term efficacy for patients with locally advanced nasopharyngeal carcinoma, without increasing the incidence of adverse reactions. Its long-term efficacy deserves further research.

12.
Artigo em Chinês | WPRIM | ID: wpr-999000

RESUMO

ObjectiveTo explore the influencing factors of different scores on predicting death risk of extremely low birth weight infants (ELBWI). MethodsA total of 186 cases of ELBWI admitted by the Children's Hospital affiliated to Nanjing Medical University and the Lishui Branch of the Affiliated Zhongda Hospital of Southeast University were admitted from January 1, 2019 to January 1, 2021, and 125 ELBWIs were finally included after screening by inclusion and exclusion criteria. There were 47 cases in the death group and 78 cases in the survival group. General data and the items of score for neonatal acute physiology version Ⅱ (SNAP-Ⅱ), simplified version of the score for neonatal acute physiology perinatal extension (SNAPPE-Ⅱ), clinical risk index for babies (CRIB), clinical risk index for babies Ⅱ (CRIB-Ⅱ) and the national critical illness score (NCIS) were collected. Univariate and multivariate analysis was performed and nomogram was evaluated using receiver operating characteristic curve (ROC). ResultsIt was found that systolic blood pressure, maximum inhaled oxygen concentration, BE value and birth weight were important factors in ELBWI mortality risk assessment [systolic blood pressure OR: 0.968, 95%CI: 0.938-0.999, P=0.043; maximum inhaled oxygen concentration OR: 1.020, 95%CI: 1.006-1.034, P=0.006; BE OR: 0.868, 95%CI: 0.786-0.959, P=0.005; birth weight OR: 0.994, 95%CI: 0.991-0.997, P=0.000]. ROC showed that the area under the curve of the above four variables is 0.71, and the 95% confidence interval is 0.610-0.799, which is better than CRIB score. ConclusionLower systolic blood pressure, higher inhaled oxygen concentration, higher BE and lower birthweight are important influencing factors to predict the death risk of ELBWI. The above four items should be included in the newly developed score assessment to obtain a more effective ELBWI prediction system.

13.
Artigo em Chinês | WPRIM | ID: wpr-982090

RESUMO

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS(n =77), MDS-AML(n =16). The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease(aGVHD) and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease(cGVHD) and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS(P =0.008)and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.


Assuntos
Masculino , Feminino , Humanos , Decitabina , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Síndromes Mielodisplásicas/complicações , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Crônica , Doença Enxerto-Hospedeiro/terapia , Recidiva
14.
Artigo em Inglês | WPRIM | ID: wpr-982479

RESUMO

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.


Assuntos
Camundongos , Animais , Proteínas Hedgehog/genética , Receptores Acoplados a Proteínas G/metabolismo , Cílios/metabolismo , Cartilagem/metabolismo , Regeneração
15.
Materials (Basel) ; 10(10)2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-29039782

RESUMO

Carbonitride (CNx) coatings have existed for several decades but are not well understood. Related studies have indicated that CNx coatings exhibit behaviors comparable to diamond-like carbon (DLC) coatings. Metal-doped CNx coatings are expected to show superior performance to single CNx coatings. In this study, a CNx coating and a group of CNx coatings with 6 at. % metal doping (W, Ti, Zr, or Cr) were prepared on biograde AISI 316L stainless steel (SS316L) substrates, and they were then characterized and studied for antibacterial and wear performance. The microstructure, constituent phase, nanohardness, adhesion, surface roughness, and contact angle were evaluated. The antimicrobial test used Staphylococcus aureus and followed the Japanese Industrial Standard JIS Z 2801:2010. Finally, the wear behavior was assessed. The results showed that the CNx coating was a composite of amorphous CNx and amorphous C structures. The metal doping caused crystalline metal carbides/nitrides to form in the CNx coatings, which weakened their overall integrity. All the coatings showed antimicrobial ability for the SS316L samples. The CNx-Zr coating, the surface of which had the highest hydrophilicity, produced the best antibacterial performance. However, the CNx-Zr coating showed lower wear resistance than the CNx-W and CNx-Ti coatings. The CNx-Ti coating with a highly hydrophilic surface exhibited the lowest antibacterial ability.

16.
Artigo em Inglês | WPRIM | ID: wpr-929133

RESUMO

Neural crest-derived mesenchymal stem cells (MSCs) are known to play an essential function during tooth and skeletal development. PRX1+ cells constitute an important MSC subtype that is implicated in osteogenesis. However, their potential function in tooth development and regeneration remains elusive. In the present study, we first assessed the cell fate of PRX1+ cells during molar development and periodontal ligament (PDL) formation in mice. Furthermore, single-cell RNA sequencing analysis was performed to study the distribution of PRX1+ cells in PDL cells. The behavior of PRX1+ cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model. Although PRX1+ cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars, their distribution in third molars is highly limited. The PDL formation is associated with a high number of PRX1+ cells; during transplanted teeth PDL reconstruction, PRX1+ cells from the recipient alveolar bone participate in angiogenesis as pericytes. Overall, PRX1+ cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.


Assuntos
Animais , Camundongos , Diferenciação Celular , Células-Tronco Mesenquimais , Dente Molar , Osteogênese/fisiologia , Ligamento Periodontal
17.
International Eye Science ; (12): 1191-1195, 2021.
Artigo em Chinês | WPRIM | ID: wpr-877381

RESUMO

@#Congenital cataract is one of the leading causes of childhood blindness and congenital membranous cataract is a rare and special type of congenital cataract. The lens fibre of congenital membranous cataract is degenerative and its cortex is absorbed gradually. Congenital membranous cataract also has another name, pseudoaphakia, due to the similar phenotype with posterior capsule opacification after cataract surgery, but without intraocular refractive power. There are few reports on congenital membranous cataract at home and abroad, and the research on the pathogenesis of congenital membranous cataract is even less. Clarifying the pathogenesis of congenital membranous cataract, especially the genetics, is very helpful for us to understand the pathogenesis of congenital cataract and the molecular mechanism of lens development.

18.
Frontiers of Medicine ; (4): 657-678, 2021.
Artigo em Inglês | WPRIM | ID: wpr-922511

RESUMO

Bone and teeth are hard tissues. Hard tissue diseases have a serious effect on human survival and quality of life. Primary cilia are protrusions on the surfaces of cells. As antennas, they are distributed on the membrane surfaces of almost all mammalian cell types and participate in the development of organs and the maintenance of homeostasis. Mutations in cilium-related genes result in a variety of developmental and even lethal diseases. Patients with multiple ciliary gene mutations present overt changes in the skeletal system, suggesting that primary cilia are involved in hard tissue development and reconstruction. Furthermore, primary cilia act as sensors of external stimuli and regulate bone homeostasis. Specifically, substances are trafficked through primary cilia by intraflagellar transport, which affects key signaling pathways during hard tissue development. In this review, we summarize the roles of primary cilia in long bone development and remodeling from two perspectives: primary cilia signaling and sensory mechanisms. In addition, the cilium-related diseases of hard tissue and the manifestations of mutant cilia in the skeleton and teeth are described. We believe that all the findings will help with the intervention and treatment of related hard tissue genetic diseases.


Assuntos
Animais , Humanos , Cílios , Homeostase , Qualidade de Vida , Transdução de Sinais
19.
Artigo em Chinês | WPRIM | ID: wpr-857516

RESUMO

The intervention of sulforaphane can reduce the risk of diabetes and its complications. It is mainly achieved by regulating nuclear factor erythroid-2-related factor 2 (Nrf2) to inhibit endothelial cell activation and improve high density lipoprotein levels. In addition, sulforaphane can bring about a marked improvement on fatty liver disease by regulating lipid metabolism. Its important pathways include the regulation of peroxisome proliferators-activated receptors y (PPARy), hormone-sensitive triglyceride lipase (HSL) and AMP-activated protein kinase (AMPK) regulation promotes lipolysis. In summary, further exploration of the mechanism of action of plant-derived functional ingredients of sulforaphane may be the key to preventing and treating diabetes and fatty liver disease.

20.
Artigo em Chinês | WPRIM | ID: wpr-827503

RESUMO

OBJECTIVE@#To establish a micellar electrokinetic capillary chromatography-based method for identification and quantitative detection of interleukin-12 (IL-12) and analysis of its unfolding process.@*METHODS@#An uncoated fused-silica capillary (inner diameter 50 μm) with a total length of 48.5 cm (40 cm to the detector) was used for the experiment. The factors influencing the separation efficiency of IL-12 were analyzed, and a standard curve of IL-12 concentration was established. The mixture of IL-12 and anti-IL-12 antibody was incubated in a water bath at 38 ℃ for 40 min, and capillary electrophoresis was then performed under the same conditions. The results were compared with those of IL-12 and anti-IL-12 antibody to identify IL-12. IL-12 and dithiothreitol (DTT) were incubated at 60 ℃ in water bath for different lengths of times, and the unfolding process of IL-12 was analyzed based on electrophoresis results of IL-12 in different states.@*RESULTS@#A micellar capillary electrophoresis on-line sweep method was established with 80 mmol/L borate (pH=9.3) containing 30 mmol/L sodium dodecyl sulfate (SDS) as the buffer solution. This system showed a good linear relationship between the peak area and the mass concentration of IL-12 with a linear correlation coefficient of 0.9991 within the linear range of 2 to 120 ng/L. As the incubation time of IL-12 and DTT prolonged, the disulfide bond of IL-12 gradually opened and resulted in distinct changes in the protein peak.@*CONCLUSIONS@#This capillary electrophoresis-based method is simple and sensitive for IL-2 analysis and allows rapid detection of changes in IL-12 content in the setting of tumors and analysis of the possible causes.

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