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1.
Nanotechnology ; 31(5): 05LT01, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31100734

RESUMO

Deformable microfluidics may be potentially used in cell manipulation, optical sensing, and imaging applications, and have drawn considerable scientific interests in the recent past. The excellent tunability of deformable microfluidic devices can provide controllable capture, deposition, and target release. We demonstrated a one-dimensional nano-sieve device to capture microparticles from suspensions. Size-selective capturing and release of micro- and nanoparticles was achieved by simply adjusting the flow rate. Almost all the microparticles were trapped in the nano-sieve device at a flow rate of 20 µl min-1. Increasing the flow rate induces a hydrodynamic deformation of the roof of the compliant device and allows most of the microparticles to pass through the channel. We also established a theoretical model based on computational fluid dynamics to reveal the relationship of the hydrodynamically induced deformation, channel dimensions, and capture efficiency that supports and rationalizes the experimental data. We have predicted the capture efficiency of micro-and nanoparticles in a nano-sieve device with various geometries and flow rates. This study may be important to the optimization of next generation deformable microfluidics for efficient micro- and nanostructure manipulations.

2.
BMC Pregnancy Childbirth ; 19(1): 439, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771540

RESUMO

BACKGROUND: Partner infection is a significant factor in preventing mother-to-child syphilis transmission. We compared pregnancy outcomes between syphilis discordant and syphilis concordant couples. METHODS: We conducted a retrospective study among 3076 syphilis-positive women who received syphilis screening together with their partners during pregnancy. Multivariate analysis was used to explore risks for abnormal outcomes in objects correcting for the major covariate factors. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated to compare pregnancy outcomes between syphilis concordant and syphilis discordant couples. RESULTS: Overall, 657 of the 3076 women were diagnosed with gestational syphilis and had a syphilis-positive partner, giving a partner concordance prevalence of 21.36%. Women in concordant couples were more likely to have higher parity, more children, late antenatal care and syphilis screening, a lower proportion of latent syphilis, and elevated serologic titers than women in discordant couples (P < 0.01 for all). Totally, 10.08% of women had adverse pregnancy outcomes. Multivariate analysis showed partners' syphilis infection (ORadj = 1.44, 95% CI: 1.10-1.89), untreated pregnancy syphilis (ORadj = 1.67, 95% CI: 1.15-2.43), and higher maternal serum titers (> 1:8) (ORadj = 1.53, 95% CI: 1.17-2.00) increased the risks of adverse pregnancy outcomes. Concordance was associated with increased risk for stillbirth (ORadj = 2.86, 95%CI:1.36-6.00), preterm birth (PTB) (ORadj = 1.38,95%CI:1.02-1.87) and low birth weight (LBW) (ORadj = 1.55, 95%CI:1.13-2.11) compared with discordance. Even among treated women, concordance was associated with increased risk for stillbirth (ORadj = 3.26, 95%CI:1.45-7.31) and LBW (ORadj = 1.52, 95%CI:1.08-2.14). Among women with one treatment course, the risks for PTB(ORadj = 1.81, 95%CI:1.14-2.88) and LBW(ORadj = 2.08, 95%CI:1.28-3.38)were also higher among concordant couples than discordant couples. Nevertheless, there were no significant differences between concordant and discordant couples in risks of stillbirth (ORadj = 2.64, 95% CI: 0.98-7.05),PTB (ORadj = 1.15, 95% CI: 0.76-1.74), and LBW(ORadj = 1.21, 95% CI: 0.78-2.02) among women with two treatment courses. CONCLUSION: Male partner coinfection increased the risks for stillbirth, PTB and LBW, particularly when gestational syphilis treatment was suboptimal. However, this risk could be reduced by adequate treatment.

3.
Connect Tissue Res ; : 1-12, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31749391

RESUMO

Aim of the study: Fluid shear stress (FSS) plays a critical role in osteoblast proliferation via extracellular signal-regulated kinase 5 (ERK5). Kruppel-like factor 4 (KLF4) knockout robustly enhances bone formation due to increased osteoblast differentiation and mineralization. However, the effect of KLF4 on osteoblast proliferation is unresolved. Therefore, the aim of our study was to investigate the effect of KLF4 on osteogenic lineage cell proliferation and the relationship between KLF4 and ERK5.Materials and methods: MC3T3-E1 cells were treated with FSS and/or KLF4 siRNA, cell viability was accessed by Edu labeling and CCK-8 assay, and proliferative gene expression were assessed by PCR array. Bone marrow stromal cells (BMSCs) were infected with adenovirus expressing KLF4 and/or constitutively active MEK5, cell viability was evaluated using crystal violet staining, colony formation assay, and cell WST1 assay. The levels of KLF4 and ERK5 phosphorylation were identified through qRT-PCR and western blot, respectively.Results: KLF4 expression was significantly down-regulated by FSS exposure, however, this was reversed by ERK5 siRNA. KLF4 overexpression inhibited colony formation efficiency and cell viability in BMSCs. Adenoviruses expressing constitutively active MEK5 increased ERK5 phosphorylation, which inhibited KLF4 expression, and promoted BMSC proliferation. FSS-induced osteoblast proliferation also involved elevation of Cyclin B2 and Cdc14b as well as repressed expression of P27.Conclusions: KLF4 negatively regulates osteogenic lineage cell proliferation, and ERK5 negatively regulates KLF4 expression and promotes osteogenic lineage cell proliferation.

4.
J Mol Diagn ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31751675

RESUMO

High WT1 expression after allogeneic hematologic stem cell transplantation (allo-HSCT) can strongly predict relapse in acute myeloid leukemia (AML). However, the cutoff values obtained were inconsistent. The precise cutoff values may be optimized through subtype analysis, and the RUNX1-RUNX1T1 fusion transcript provides an ideal reference. RUNX1-RUNX1T1 and WT1 transcript levels were simultaneously measured in 1,299 bone marrow samples serially collected from 176 t(8;21) AML patients after receiving allo-HSCTfor. The upper limit of the normal bone marrow WT1 level was 0.6%, previously reported to be the cutoff value for significant relapse prediction in AML as a whole. The cutoff values 0.6%, 1.2%, and 1.8% for WT1 significantly differentiated patients in relapse after allo-HSCT. Nevertheless, both patients with WT1 levels 0.6% to 1.2% and those with levels between 1.2% to 1.8% post-HSCT had a similar cumulative incidence of relapse rates as those with a continuous WT1 level ≤0.6% and both were significantly lower than that of patients with a WT1 level >1.8%. WT1 expression was significantly related to the RUNX1-RUNX1T1 transcript levels at WT1 levels >1.8% but not at levels 0.6% to 1.2% and 1.2% to 1.8%. Therefore, subgroup analysis can optimize the relapse prediction cutoff value for WT1 expression, and a cutoff level of 1.8% more accurately differentiates t(8;21) AML patients in relapse after allo-HSCT than the cutoff level of 0.6%.

5.
Paediatr Anaesth ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31743521

RESUMO

BACKGROUND: The rigid cricoid cartilage is functionally the narrowest portion of the larynx. There is some controversy over the shape of the pediatric cricoid cartilage in the transverse plane. It is important to understand the development of the cricoid cartilage so that ETTs can be used more safely. AIM: To determine changes in the internal diameter and shape of the cricoid cartilage during development and explore the implications of those changes for the selection of ETT type and size for children. METHODS: The cervical computed tomography scans were reviewed in patients aged 1 year to 20 years. After performing the multiplanar reconstruction and correcting the slant, the transverse and anteroposterior internal diameters of the inlet and outlet of the cricoid cartilage were measured, respectively. The angle between the arch and lamina of the cricoid cartilage in the middle sagittal plane was measured. The ratios of transverse to anteroposterior diameter for the inlet and outlet of the cricoid cartilage were calculated, respectively. RESULTS: In females, the internal diameters of the cricoid cartilage increased linearly with age. In males, the internal diameters of the cricoid cartilage exhibited a growth spurt during adolescence. The transverse diameter of the inlet was the smallest diameter of the cricoid cartilage and the predicting formula of the transverse diameter of the inlet for children aged 1 to 12 was: 0.4 × age (year) + 5.1, R2 = 0.758. The angle between the arch and lamina of the cricoid cartilage and the ratios of transverse to anteroposterior diameter correlated weakly with age. CONCLUSION: The transverse inner diameter of the inlet is the smallest diameter of the cricoid cartilage. The "funnel shape" of the cricoid cartilage remains unchanged during development. The outer diameter should be considered when selecting an endotracheal tube.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31711718

RESUMO

The new compound of 4-(bis(5-bromo-1H-indol-3-yl)methyl)phenol (BMP) is synthesized through a one-step reaction. Then the inhibition mechanism of inhibitor on copper surface is investigated by Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy (XPS). Moreover, scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS) is employed to characterize the surface morphology of studied copper and electrochemical impendence spectroscopy (EIS) is carried out to study the inhibition efficiency of the inhibitor. From these results obtained, it can be concluded that BMP is considered as corrosion inhibitor for copper in sulfuric solution.

7.
Br J Haematol ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696939

RESUMO

Donor selection for older leukaemia patients undergoing haematopoietic cell transplant (HCT) is not well defined: outcomes might be improved with a younger offspring donor rather than an older human leukocyte antigen (HLA)-matched sibling donor (MSD). We extended our multicentre dataset. A total of 185 acute leukaemia patients (≥ 50 years) transplanted in first complete remission who received HCT from offspring (n = 62) or MSD (n = 123) were included. A 1:1 ratio matched-pair analysis was performed. We were able to match 54 offspring with 54 MSD patients. Outcomes were compared between the two matched-pair groups. The cumulative incidence of grade II/IV acute graft-versus-host disease (GVHD) (26% vs. 35%; P = 0·23) and chronic GVHD (37% vs. 24%; P = 0·19) was comparable between groups (MSD vs. offspring). The lower three-year transplant-related mortality (9% vs. 26%; P = 0·023) and relapse incidence (6% vs. 17%; P = 0·066) resulted in higher overall survival (85% vs. 58%; P = 0·003) and leukaemia-free survival (LFS) (85% vs. 56%; P = 0·001) in offspring HCT compared with that in MSD HCT. These data might favour a young offspring over an older MSD in patients >50 years. The current analyses confirm that non-HLA donor characteristics, such as kinship and donor age, rather than HLA disparity, predominantly influence survival in older acute leukaemia patients.

8.
Br J Haematol ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31725190

RESUMO

We explored the prognostic factors for children with very high-risk (VHR) Philadelphia chromosome (Ph) negative B-cell acute lymphoblastic leukaemia (B-ALL) and compared the therapeutic effects of intensive chemotherapy and unmanipulated haploidentical haematopoietic stem cell transplantation (haplo-HSCT) as post-remission treatment in these patients undergoing first complete remission (CR1). A total of 104 paediatric patients with VHR B-ALL in CR1 were retrospectively enrolled in this study, including 42 receiving unmanipulated haplo-HSCT (Group A) and 62 receiving ongoing chemotherapy (Group B). Estimated 3-year overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) at 36·2 months median follow-up were 69·5 ± 4·7%, 63·5 ± 4·8% and 32·4 ± 4·7%, respectively. Maintenance of persistent positive or conversion from negative to positive of measurable residual disease (MRD) and chemotherapy were independent risk factors associated with inferior long-term survival and higher CIR. OS, DFS, and CIR differed significantly between the groups in patients with persistent positive or negative-to-positive MRD. Haplo-HSCT may be an option for children with VHR Ph-negative B-ALL in CR1, especially for patients with persistent positive or negative-to-positive MRD, and could achieve better survival than intensive chemotherapy as post-remission treatment.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31704470

RESUMO

Basiliximab has been used successfully as a second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in adult patients after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) but has not been studied separately in the pediatric setting. We retrospectively reviewed 100 pediatric patients after haplo-HSCT receiving basiliximab for grades II (57%), III (27%), and IV (16%) SR-aGVHD between January 2015 and December 2017. The median number of basiliximab doses was 4 (range, 2-9). The day 28 overall response rate (ORR) was 85%, with complete response (CR) in 74% of patients, partial response (PR) in 11% of patients, and no response in 15% of patients. The day 28 ORR was 94.6% in skin SR-aGVHD, 81.6% in gut SR-aGVHD, and 66.7% in liver SR-aGVHD. Infectious complications included bacterial infection (11%), presumed or documented fungal infections (7%), CMV viremia (53%), EBV viremia (11%), HHV-6 viremia (7%), and HSV viremia (1%). The 3-year overall survival (OS), disease-free survival (DFS), nonrelapse mortality (NRM), and relapse rates between responders and nonresponders were 81.3% vs. 46.7% (P<0.001), 79.0% vs. 46.7% (P=0.001), 6.1% vs. 33.3% (P<0.001), and 14.9% vs. 20.0% (P=0.46), respectively. We conclude that basiliximab is an effective second-line agent for pediatric patients with SR-aGVHD after haplo-HSCT, particularly for skin SR-aGVHD.

10.
World J Surg Oncol ; 17(1): 193, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733657

RESUMO

BACKGROUND: The aim of this study is to determine pathological factors that increase the risk of LNM and indicate poor survival of patients diagnosed with endometrial cancer and treated with surgical staging. METHOD: Between January 2010 and November 2018, we enrolled 874 eligible patients who received staging surgery in the First Affiliated Hospital of Anhui Medical University. The roles of prognostic risk factors, such as age, histological subtype, tumor grade, myometrial infiltration, tumor diameter, cervical infiltration, lymphopoiesis space invasion (LVSI), CA125, and ascites, were evaluated. Multivariable logistic regression models were used to identify the predictors of LNM. Kaplan-Meier and COX regression models were utilized to study the overall survival. RESULTS: Multivariable regression analysis confirmed cervical stromal invasion (OR 3.412, 95% CI 1.631-7.141; P < 0.01), LVSI (OR 2.542, 95% CI 1.061-6.004; P = 0.04) and ovarian metastasis (OR 6.236, 95% CI 1.561-24.904; P = 0.01) as significant predictors of nodal dissemination. Furthermore, pathological pattern (P = 0.03), myometrial invasion (OR 2.70, 95% CI 1.139-6.40; P = 0.01), and lymph node metastasis (OR 9.675, 95% CI 3.708-25.245; P < 0.01) were independent predictors of decreased overall survival. CONCLUSIONS: Cervical invasion, lymphopoiesis space invasion, and ovarian metastasis significantly convey the risk of LNM. Pathological type, myometrial invasion, and lymph node metastasis are all important predictors of survival and should be scheduled for completion when possible in the surgical staging procedure.

11.
Intern Med J ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31707748

RESUMO

BACKGROUND: Malnutrition is one of the most common complications among dialysis patients. The Geriatric Nutritional Risk Index (GNRI) is rarely used in dialysis patients, especially peritoneal dialysis (PD). AIM: To use the GNRI to evaluate the initial nutritional state of PD patients and to examine the association between the GNRI and mortality in chronic PD patients. METHODS: We retrospectively examined the medical records at our centre to identify all adults (≥18 years) who had undergone PD for over 3 months before recruitment from January 2005 to December 2017. The correlation between the GNRI and mortality was examined by Kaplan-Meier and Cox proportional hazards analyses. RESULTS: A total of 1804 patients were enrolled in the study. Significant correlations were noted between the initial GNRI and Charlson index, uric acid, blood calcium, potassium, triglycerides, low-density lipoprotein cholesterol, haemoglobin and so on. Multivariate Cox proportional hazards analyses demonstrated that the GNRI was associated with all-cause mortality (HR = 0.96, P < 0.001, 95% CI:0.95-0.98) after adjustment. Compared with the lowest GNRI group, all-cause mortality decreased significantly for each level of GNRI after adjusting for various influencing factors, and the mortality risk of the highest GNRI grade decreased by 66%. The Kaplan-Meier analysis survival rate was significantly different among the 4 groups in terms of all-cause mortality and cardiovascular and cerebrovascular mortality (log-rank test, P < 0.05). CONCLUSIONS: These results demonstrated that the GNRI is significantly associated with mortality and can be a simple, clinically useful marker for the assessment of nutritional status in PD patients. This article is protected by copyright. All rights reserved.

12.
Blood Adv ; 3(21): 3406-3418, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714962

RESUMO

Thrombocytopenia is associated with life-threatening bleeding and is common in myelodysplastic syndromes (MDS). Robust molecular prognostic biomarkers need to be developed to improve clinical decision making for patients with MDS with thrombocytopenia. Wilms tumor 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are promising immunogenic antigen candidates for immunotherapy, and their clinical effects on patients with MDS with thrombocytopenia are still not well understood. We performed a multicenter observational study of adult patients with MDS with thrombocytopenia from 7 different tertiary medical centers in China. We examined bone marrow samples collected at diagnosis for WT1 and PRAME transcript levels and then analyzed their prognostic effect for patients with MDS with thrombocytopenia. In total, we enrolled 1110 patients diagnosed with MDS with thrombocytopenia. Overexpression of WT1 and PRAME was associated with elevated blast percentage, worse cytogenetics, and higher Revised International Prognostic Scoring System (IPSS-R) risk. Further, both WT1 and PRAME overexpression were independent poor prognostic factors for acute myeloid leukemia evolution, overall survival, and progression-free survival. Together, the 2 genes overexpression identified a population of patients with MDS with substantially worse survival. On the basis of WT1 and PRAME transcript levels, patients with MDS with IPSS-R low risk were classified into 2 significantly divergent prognostic risk groups: a low-favorable group and a low-adverse group. The low-adverse group had survival similar to that of patients in the intermediate-risk group. Our study demonstrates that the evaluation of WT1/PRAME transcript analysis may improve the prognostication precision and better risk-stratify the patients.

13.
iScience ; 21: 84-94, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31655258

RESUMO

Epithelia of the oral cavity exhibit variations in morphologies and turnover rates. Are these differences related to environment or to region-specific stem cell populations? A lineage-tracing strategy allowed visualization of Wnt-responsive cells, and their progeny, in the hard and soft palates. In both anatomic locations, Wnt-responsive basal cells self-renewed and gave rise to supra-basal cells. Palatal injuries triggered an enlargement of this population, and their descendants were responsible for wound re-epithelialization. Compared with the hard palate, soft palate stem cells exhibited an earlier, more robust burst in proliferation, culminating in significantly faster repair. Thereafter, excess Wnt-responsive basal cells were removed, and stem cell numbers were restored back to homeostatic level. Thus, we uncovered a stem cell population in oral mucosa, and its relative abundance is correlate with the rate of oral wound healing. Besides the activation during injury, an endogenous mechanism exists to constrain the stem cell pool after repair.

14.
Clin Neuroradiol ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31578601

RESUMO

PURPOSE: The aim of this study was to investigate resting state functional connectivity alterations within the main brain networks in neuromyelitis optica spectrum disorder (NMOSD) and their associations with disease duration, disability and cognitive dysfunction progression. METHODS: Resting state functional magnetic resonance imaging (rs-fMRI), clinical and neuropsychological evaluations were obtained from 41 NMOSD patients and 41 healthy controls. Seed-voxel functional connectivity was analyzed in seven major hubs, including the default mode network, dorsal attention network, visual network, sensorimotor network, cerebellar network, thalamic network and reward-emotion network. Abnormalities of functional connectivity and correlations with disease duration, scores of the expanded disability status scale (EDSS), mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were further explored. RESULTS: Compared with healthy controls, NMOSD patients showed increased functional connectivity in the default mode network, dorsal attention network and thalamic network, while decreased in the visual network and cerebellum networks. At the regional level, increased functional connectivity involved the right superior temporal gyrus, left fusiform gyrus, left inferior parietal lobule, bilateral middle frontal gyrus and right precuneus, whereas functional connectivity was decreased in the right parahippocampal gyrus and left precuneus. Functional connectivity reduction in the right parahippocampal gyrus positively correlated with disease duration (r = 0.488, p = 0.001) and negatively correlated with MoCA scores (r = -0.330, p = 0.035). CONCLUSION: The study demonstrated functional alterations in the rs-fMRI of NMOSD, which provide a novel insight into the large-scale selective functional reorganization and could be useful to reveal the characteristics of the physiological mechanism.

15.
Br J Ophthalmol ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31630094

RESUMO

BACKGROUND: Leber congenital amaurosis (LCA) and early onset severe retinal dystrophy (EOSRD) are clinically and genetically heterogeneous inherited retinal disorders that cause severe visual impairment in children. The objective of this study was to describe the mutation profile and phenotypic characteristics in Chinese patients with LCA or EOSRD. METHODS: Retrospective consecutive case series (2010-2017) study was performed in 148 probands (91 with LCA and 57 with EOSRD). All patients underwent ophthalmic evaluation. Mutations were revealed using targeted next-generation sequencing, followed by Sanger DNA-sequencing and real-time quantitative PCR analysis. RESULTS: We identified two diseasing-causing mutations in 88 unrelated patients, heterozygous autosomal dominant mutations in 11 probands and X-linked hemizygous mutations in 11 patients, for an overall mutation detection rate of 74.3% (110/148). We detected 158 different disease-causing mutations involving 14 LCA genes, 16 retinitis pigmentosa or cone-rod dystrophy genes and 3 syndromic retinal dystrophy genes. Of these 158 mutations, 98 were novel. The most common mutation was p.Q141X of AIPL1, with a gene-specific allele frequency of 60%. The first five most frequently mutated genes were AIPL1 (11.0%), RPGRIP1 (8.8%) and CEP290, GUCY2D and RPE65 (each 7.7%) in the patients with LCA and RPGR (12.3%), CRB1 (10.5%), RPE65 (10.5%), RDH12 (7.0%) and RP2 (5.3%) in the patients with EOSRD. CONCLUSIONS: Our results revealed that the mutation spectrum of patients with LCA differs from that of the patients with EOSRD and established the configuration of the mutation frequencies for each LCA gene in Chinese patients, thereby providing essential information for future genetic counselling and gene therapy.

16.
J Biol Chem ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653699

RESUMO

Peroxisome proliferator-activated receptor γ (PPARγ) is the central regulator of adipogenesis, and its dysregulation is linked to obesity and metabolic diseases. Identification of the factors that regulate PPARγ expression and activity is therefore crucial for combating obesity. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with a known role in xenobiotic detoxification. Recent studies have suggested that AhR also plays essential roles in energy metabolism. However, the detailed mechanisms remain unclear. We previously reported that experiments with adipocyte-specific Cullin 4b (Cul4b)-knockout mice showed that CUL4B suppresses adipogenesis by targeting PPARγ. Here, using immunoprecipitation, ubiquitination, real-time PCR and Gst-pulldown assays, we report that AhR functions as the substrate receptor in CUL4B-RING E3 ubiquitin ligase (CRL4B) complex and is required for recruiting PPARγ. AhR overexpression reduced PPARγ stability and suppressed adipocyte differentiation, and AhR knockdown stimulated adipocyte differentiation in 3T3-L1 cells. Furthermore, we found that two lysine sites on residues 268 and 293 in PPARγ are targeted for CRL4B-mediated ubiquitination, indicating cross-talk between acetylation and ubiquitination. Our findings establish a critical role of AhR in regulating PPARγ stability and suggest that the AhR-PPARγ interaction may represent a potential therapeutic target for managing metabolic diseases arising from PPARγ dysfunction.

17.
Int J Med Inform ; 132: 103985, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31627032

RESUMO

OBJECTIVE: Breast cancer is the most common malignant tumor among women. The diagnosis and treatment information of breast cancer patients is abundant in multiple types of clinical fields, including clinicopathological data, genotype and phenotype information, treatment information, and prognosis information. However, current studies are mainly focused on extracting information from one specific type of clinical field. This study defines a comprehensive information model to represent the whole-course clinical information of patients. Furthermore, deep learning approaches are used to extract the concepts and their attributes from clinical breast cancer documents by fine-tuning pretrained Bidirectional Encoder Representations from Transformers (BERT) language models. MATERIALS AND METHODS: The clinical corpus that was used in this study was from one 3A cancer hospital in China, consisting of the encounter notes, operation records, pathology notes, radiology notes, progress notes and discharge summaries of 100 breast cancer patients. Our system consists of two components: a named entity recognition (NER) component and a relation recognition component. For each component, we implemented deep learning-based approaches by fine-tuning BERT, which outperformed other state-of-the-art methods on multiple natural language processing (NLP) tasks. A clinical language model is first pretrained using BERT on a large-scale unlabeled corpus of Chinese clinical text. For NER, the context embeddings that were pretrained using BERT were used as the input features of the Bi-LSTM-CRF (Bidirectional long-short-memory-conditional random fields) model and were fine-tuned using the annotated breast cancer notes. Furthermore, we proposed an approach to fine-tune BERT for relation extraction. It was considered to be a classification problem in which the two entities that were mentioned in the input sentence were replaced with their semantic types. RESULTS: Our best-performing system achieved F1 scores of 93.53% for the NER and 96.73% for the relation extraction. Additional evaluations showed that the deep learning-based approaches that fine-tuned BERT did outperform the traditional Bi-LSTM-CRF and CRF machine learning algorithms in NER and the attention-Bi-LSTM and SVM (support vector machines) algorithms in relation recognition. CONCLUSION: In this study, we developed a deep learning approach that fine-tuned BERT to extract the breast cancer concepts and their attributes. It demonstrated its superior performance compared to traditional machine learning algorithms, thus supporting its uses in broader NER and relation extraction tasks in the medical domain.

18.
BMC Cancer ; 19(1): 939, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604469

RESUMO

BACKGROUND: This preliminary study aimed to examine the feasibility of sentinel lymph node biopsy (SLNB) using contrast-enhanced ultrasound (CEUS) vs. indocyanine green fluorescence (ICG), combined with blue dye in patients with breast cancer. METHODS: This was a retrospective study of consecutive female patients with invasive stage I-III (based on pre-operative physical examination and imaging) primary breast cancer at the Peking Union Medical College Hospital between 01/2013 and 01/2015 who underwent preoperative SLNB by ICG + blue dye or CEUS + blue dye. The numbers of detected SLNs, detection rates, and recurrence-free survival (RFS) rates were compared between the two groups. RESULTS: A total of 443 patients were included. The detection rates of SLNs in the CEUS + blue dye and ICG + blue dye groups were 98.4 and 98.1%, respectively (P = 0.814). The average numbers of SLNs detected per patient showed no significant difference between the two groups (3.06 ± 1.33 and 3.12 ± 1.31 in the CEUS + blue dye and ICG + blue dye groups, respectively; P = 0.659). After a median follow-up of 46 months, five patients in the CEUS + blue dye group and 15 in the ICG + blue dye group had recurrence. RFS rates showed no significant difference (P = 0.55). CONCLUSION: This preliminary study suggests that CEUS + blue dye and ICG + blue dye are both feasible for SLN detection in breast cancer.

19.
Plant Physiol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649110

RESUMO

Cyanobacteria experience drastic changes in their carbon metabolism under daily light-dark cycles. During the day, the Calvin-Benson cycle fixes CO2 and diverts excess carbon into glycogen storage. At night, glycogen is degraded to support cellular respiration. The dark-light transition represents a universal environmental stress for cyanobacteria and other photosynthetic lifeforms. Recent studies revealed the essential genetic background necessary for the fitness of cyanobacteria during diurnal growth. However, the metabolic processes underlying the dark-light transition are not well understood. In this study, we observed that glycogen metabolism supports photosynthesis in the cyanobacterium Synechococcus elongatus PCC 7942 when photosynthesis reactions start upon light exposure. Compared to the wild type, the glycogen mutant (∆glgC) showed a reduced photosynthetic efficiency and a slower P700+ re-reduction rate when photosynthesis starts. Proteomic analyses indicated that glycogen is degraded through the oxidative pentose phosphate (OPP) pathway during the dark-light transition. We confirmed that the OPP pathway is essential for the initiation of photosynthesis, and further showed that glycogen degradation through the OPP pathway contributes to the activation of key Calvin-Benson cycle enzymes by modulating NADPH levels. This strategy stimulates photosynthesis in cyanobacteria following dark respiration, and stabilizes the Calvin-Benson cycle under fluctuating environmental conditions, thereby offering evolutionary advantages for photosynthetic organisms using the Calvin-Benson cycle for carbon fixation.

20.
J Hematol Oncol ; 12(1): 87, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477147

RESUMO

BACKGROUND: Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. METHODS: We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. RESULTS: Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0-1), or moderate graft mononuclear cell (MNC) counts (6-10 × 108/kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0-1). CONCLUSIONS: Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA.

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