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1.
Virol Sin ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001388

RESUMO

Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized children in the Children's Hospital Affiliated to the Capital Institute of Paediatrics in Beijing. To investigate whether this outbreak of HAdV was related to nosocomial infections or the result of community infections, we collected respiratory specimens from patients with acute respiratory infections in a respiratory ward during June to December 2018, and screened for respiratory viruses. Among 1,840 cases included, 95 (5.2%, 95/1840) were positive for HAdV and 81 were genotyped based on phylogenetic analysis, including seven as HAdV-1 (8.6%), 30 HAdV-3 (37.0%), two HAdV-6 (2.5%), and 42 HAdV-7 (51.9%). More HAdV-positive samples were collected in August (4.7%, 12/255), September (15.0%, 41/274) and October (6.9%, 17/247), with a peak in September 2018. By combining the results of HAdV phylogenetic analysis with clinical data of patients, there were 77 cases (4.2%, 77/1840; 81.1%, 77/95) excluded from nosocomial infections, eight cases representing possible infections transmitted by visitors or attending parents, three cases without sequences that might have been due to infection transmitted by roommates positive for HAdV, one case of a roommate without an HAdV sequence, and six cases that shared highly homologous sequences with those of their roommates, for which nosocomial infections might be considered. In conclusion, genotyping of HAdVs based on phylogenetic analysis combined with clinical information provides a powerful method to distinguish nosocomial infections from community acquired infection, especially when tracing the origins of nosocomial infections.

2.
Nat Commun ; 11(1): 5372, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097724

RESUMO

Chiral aldehyde catalysis is a burgeoning strategy for the catalytic asymmetric α-functionalization of aminomethyl compounds. However, the reaction types are limited and to date include no examples of stereodivergent catalysis. In this work, we disclose two chiral aldehyde-catalysed diastereodivergent reactions: a 1,6-conjugate addition of amino acids to para-quinone methides and a bio-inspired Mannich reaction of pyridinylmethanamines and imines. Both the syn- and anti-products of these two reactions can be obtained in moderate to high yields, diastereo- and enantioselectivities. Four potential reaction models produced by DFT calculations are proposed to explain the observed stereoselective control. Our work shows that chiral aldehyde catalysis based on a reversible imine formation principle is applicable for the α-functionalization of both amino acids and aryl methylamines, and holds potential to promote a range of asymmetric transformations diastereoselectively.

3.
Cell ; 182(5): 1214-1231.e11, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32888494

RESUMO

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.

4.
Ann Clin Transl Neurol ; 7(10): 2010-2018, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32951348

RESUMO

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is an adult-onset fatal neurodegenerative disease which lacks identified biological markers. A label-free plasma surface-enhanced Raman spectroscopy (SERS) method was developed to explore a simple and noninvasive test for ALS. METHODS: ALS patients were enrolled serially and plasma samples were collected at the time of diagnosis prior to the start of ALS treatment. SERS spectra were recorded using a Renishaw micro-Raman system. RESULTS: To exclude the interference by varying disease severity, we enrolled three groups of ALS patients, including ALS-1 (n = 60; ALSFRS-R ≥ 42 and time interval ≤ 12 months), ALS-2 (n = 61; ALSFRS-R < 42 and time interval ≤ 12 months), and ALS-3 (n = 61; ALSFRS-R ≥ 38 and time interval> 12 months). The SERS spectra were analyzed using principal component analysis (PCA), which showed that ALS-1, ALS-2, ALS-3, and control groups were separated significantly. Then, decision tree (DT) models and receiver operating characteristic curves were employed and identified that bands at 722 and 739 cm-1 , and ratios of 635-722 cm-1 and 635-739 cm-1 were able to distinguish ALS from controls significantly. Finally, we highlighted six metabolism pathways correlated with ALS, including phenylalanine-tyrosine-tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, pantothenate and CoA biosynthesis, porphyrin and chlorophyll metabolism, and pyrimidine metabolism. INTERPRETATION: Plasma SERS could be a promising tool for the detection of ALS. The bands at 722 and 739 cm-1 , and the ratios of 635-722 cm-1 and 635-739 cm-1 could serve as potential indicator for ALS.

5.
MedEdPORTAL ; 16: 10945, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32908950

RESUMO

Introduction: Musculoskeletal (MSK) disorders are very common, but suboptimal teaching of MSK medicine occurs and expert clinicians agree that MSK physical examination (PE) skills can be confusing and complicated for medical students. An innovative approach in introductory teaching of MSK PE skills was developed using constructivist theory for second-year medical students. Methods: We implemented the MSK PE curriculum innovation in the second year of a four-year MD program, utilizing a standard framework with spaced practice and clinician coaching. We evaluated this curriculum by comparing the innovation group (n = 123) to a historical control group (n = 134) using an anonymous survey and OSCE station scores. Data analysis included repeated measures analysis of variance comparing students' self-confidence in MSK PE to students' self-confidence in other systems-based PEs, as well as independent t-test comparisons of self-confidence scores and MSK-specific OSCE station scores between the historical and innovation groups. Results: The mean self-assessed confidence of the historical group was significantly lower for the MSK PE than all other PEs (p < 0.001), except for the neurological PE. Significant improvement in MSK PE self-confidence was noted with the innovation group (t(259) = -4.05, p < 0.001). OSCE scores significantly improved in MSK-specific stations, with medium to large effect size across the different stations. Discussion: We successfully used a framework of deconstruction, repetition, and spaced practice to develop fundamental MSK PE skills in preclerkship medical students. This curriculum structure provides an effective example for teaching introductory MSK PE skills to early medical learners.

6.
Diabetologia ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880686

RESUMO

AIMS/HYPOTHESIS: Adiponectin stimulates mitochondrial biogenesis through peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), a major regulator of mitochondrial biogenesis. MOTS-c (mitochondrial open reading frame of the 12S rRNA) is a biologically active mitochondrial-derived peptide encoded by mitochondrial DNA. It influences the mechanisms of obesity and diabetes. We hypothesised that the adiponectin pathway may regulate the production and/or secretion of MOTS-c in skeletal muscle. We aimed to determine whether exercise and adiponectin affect MOTS-c to improve insulin resistance in mice. METHODS: To investigate this hypothesis, we used wild-type C57BL/6 mice subjected to high-fat diet, an exercise regimen, and i.p. injection of recombinant mouse adiponectin (Acrp30) or MOTS-c, and adiponectin knockout (Adipoq-/-) mice (C57BL/6 background) subjected to i.p. injection of Acrp30. C2C12 myotubes were also treated with sirtuin 1 (SIRT1) inhibitor, PGC-1α inhibitor, SIRT1 activator, plasmid-expressed active APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper), pcDNA-SIRT1, or siRNA against APPL1, SIRT1 or PGC-1α. RESULTS: In Adipoq-/- mice, MOTS-c levels in the plasma and skeletal muscle were downregulated. In C2C12 myotubes, adiponectin increased the mRNA expression of MOTS-c. APPL1 protein level following adiponectin treatment positively correlated with MOTS-c protein and mRNA levels in C2C12 myotubes. SIRT1 overexpression increased the adiponectin-induced mRNA and protein expression of MOTS-c, SIRT1 and PGC-1α. Pharmacologic and genetic inhibition of PGC-1α suppressed the increases in MOTS-c mRNA and protein levels induced by SIRT1 overexpression. In mice, plasma and skeletal muscle MOTS-c levels were significantly downregulated following high-fat-diet. Exercise and i.p. Acrp30 or MOTS-c increased MOTS-c levels and adiponectin mRNA and protein expression in the plasma and skeletal muscle. CONCLUSIONS/INTERPRETATION: Our findings showed that the APPL1-SIRT1-PGC-1α pathway regulates the production and/or secretion of skeletal muscle MOTS-c by mediating adiponectin signalling. Our study provides an insight into the cellular and molecular pathways underlying the pathogenesis of diabetes and shows that MOTS-c is a potential novel therapeutic target in the treatment of diabetes. Graphical abstract.

7.
Radiat Oncol ; 15(1): 211, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873308

RESUMO

BACKGROUND: The goal of this study was to assess small bowel motion and explore the feasibility of using peritoneal space (PS) to replace bowel loops (BL) via the dose constraint method to spare the small bowel during intensity-modulated radiotherapy (IMRT) for rectal cancer. METHODS: A total of 24 patients with rectal cancer who underwent adjuvant or neoadjuvant radiotherapy were selected. Weekly repeat CT scans from pre-treatment to the fourth week of treatment were acquired and defined as Plan, 1 W, 2 W, 3 W, and 4 W. The 4 weekly CT scans were co-registered to the Plan CT, BL and PS contours were delineated in all of the scans, an IMRT plan was designed on Plan CT using PS constraint method, and then copied to the 4 weekly CT scans. The dose-volume, normal tissue complication probability (NTCP) of the small bowel and their variations during treatment were evaluated. RESULTS: Overall, 109 sets of CT scans from 24 patients were acquired, and 109 plans were designed and copied. The BL and PS volumes were 250.3 cc and 1339.3 cc. The V15 of BL and PS based plan of pre-treatment were 182.6 cc and 919.0 cc, the shift% of them were 28.9 and 11.3% during treatment (p = 0.000), which was less in the prone position than in the supine position (25.2% vs 32.1%, p = 0.000; 9.9% vs 14.9%, p = 0.000). The NTCPC and NTCPA based plan of pre-treatment were 2.0 and 59.2%, the shift% during treatment were 46.1 and 14.0% respectively. Majority of BL's Dmax and V15 were meet the safety standard during treatment using PS dose limit method except 3 times (3/109) of V15 and 5 times of Dmax (5/109). CONCLUSIONS: This study indicated that small bowel motion may lead to uncertainties in its dose volume and NTCP evaluation during IMRT for rectal cancer. The BL movements were significantly greater than PS, and the prone position was significantly less than the supine position. It is feasibility of using PS to replace BL to spare the small bowel, V15 < 830 cc is the dose constraint standard.

8.
Diabetes Ther ; 11(10): 2341-2355, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32870466

RESUMO

INTRODUCTION: Postprandial hyperglycemia is independently associated with many adverse complications, while diets with a low glycemic load are beneficial in improving post-meal glucose levels. This study aims to determine if mobile-app-based low-carbohydrate dietary guidance will reduce exposure to postprandial hyperglycemia in adults with prediabetes. METHODS: This single-blind, randomized controlled pilot study included 100 participants (39 men; mean age 53.6 ± 11.9 years) and was performed in the PKU Care CNOOC Hospital, China. The intervention group (n = 57) received low-carbohydrate dietary guidance through a moblie app (CAReNA) for 3 months, while the control group (n = 43) only received health education on a diabetic diet. The primary outcome was change in time of postprandial hyperglycemia between baseline and 3 months. RESULTS: The study revealed that the mean time in postprandial hyperglycemia (> 7.8 mmol/l [140 mg/dl]) monitored by flash glucose monitoring changed from 3.27 h/day at baseline to 2.34 h/day at 3 months in the intervention group and from 3.08 h/day to 2.96 h/day in the control group, with a between-group difference of - 0.81 h/day (P < 0.05). Fasting plasma glucose and glycated hemoglobin (HbA1c) in the intervention group decreased significantly, although no significant difference was seen between the two groups. Compared with the control group, the intervention group had a significant decrease in anthropometric and body composition measurements as well as triglycerides. CONCLUSION: The mobile-app-based low-carbohydrate dietary guidance effectively reduced the time spent in postprandial hyperglycemia in adults with prediabetes. This new type of nutritional management has beneficial effects on people with prediabetes and needs further research. CLINICAL TRIAL REGISTRATION: ChiCTR1900024880.

9.
Biochem Biophys Res Commun ; 529(3): 659-665, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32736689

RESUMO

Cytidine deaminase (CDA) catalyzes the (deoxy)cytidine deamination to (deoxy)uridine, which involves in the catabolic and salvage pathways of pyrimidine nucleotides in plants. CDA serves as a prototype of the cytidine deaminase superfamily that contains a number of RNA editing enzymes. Arabidopsis thaliana has only one functional CDA, AtCDA1. We solved the crystal structures of AtCDA1, which is a dimeric zinc-containing enzyme and each protomer consists of an N-terminal zinc-binding catalytic domain and a C-terminal non-catalytic domain. Both domains adopt a typical α/ß/α sandwich fold. In vitro biochemical assays showed that the ribose moiety of cytidine is required for ligand binding, and structural analyses revealed a conserved catalytic mechanism is adopted by AtCDA1.

10.
Sci Rep ; 10(1): 13675, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32792593

RESUMO

Currently, nanoparticles (NPs) for cancer photothermal therapy (PTT) have limited in vivo clearance, lack targeting ability and have unsatisfactory therapeutic efficiency. Herein, we report a dual-targeting and photothermally triggered nanotherapeutic system based on superparamagnetic iron oxide (Fe3O4) and indocyanine green (ICG)-entrapped poly-lactide-co-glycolide modified by ZOL (PLGA-ZOL) NPs (ICG/Fe3O4@PLGA-ZOL) for PTT of breast cancer tibial metastasis, which occurs frequently in the clinic and causes challenging complications in breast cancer. In this system, both ICG and Fe3O4 can convert light into heat, while NPs with Fe3O4 and ZOL can be attracted to a specific location in bone under an external magnetic field. Specifically, the dual-targeting and double photothermal agents guaranteed high accumulation in the tibia and perfect PTT efficiency. Furthermore, the in vivo studies showed that ICG/Fe3O4@PLGA-ZOL NPs have extraordinary antitumor therapeutic effects and that these NPs can be accurately located in the medullary cavity of the tibia to solve problems with deep lesions, such as breast cancer tibial metastasis, showing great potential for cancer theranostics.

11.
Bone ; : 115617, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32853852

RESUMO

Bone mesenchymal stem cells (BMSCs) are progenitor cells isolated from bone marrow, which keep potential to differentiate into several kinds of cells including osteoblasts and adipocytes. A dynamic mutual regulation exists between osteogenesis and adipogenesis processes. Long non-coding RNA (lncRNA) performs diverse functions in biological activities including regulation of BMSCs commitment. Evidence has shown that lncRNA regulates key signaling pathways including TGFß/BMP, Wnt and Notch pathways, and several transcription factors in BMSCs differention. Dysregulation of lncRNA in BMSCs leads to disruption of osteo-adipogenesis difffrentiation and results in impairment of bone homeostasis. In this review, we focus on the role of lncRNA in several critical signaling pathways that involved in regulation of osteo-adipogenesis of BMSC and prospects the potential clinical application of lncRNA.

12.
J Chromatogr A ; 1627: 461382, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823094

RESUMO

A method is described for the functionalization of magnetic carbon nanotubes to recognize aristolochic acid Ⅰ and Ⅱ. 3-Glycidyloxypropyltrimethoxysilane was used as a coupling agent to immobilize adenine on a solid support. The morphology and structure of adenine-coated magnetic carbon nanotubes was investigated using transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) and a vibrating sample magnetometer (VSM). The adsorption performance of the adenine-coated magnetic carbon nanotubes was evaluated via adsorption isotherms, the kinetics and selectivity tests. The adsorption capacity of the adenine-functionalized sorbent for aristolochic acid Ⅰ was determined to be 24.5 µg mg-1. By combining magnetic solid phase extraction with HPLC detection, a method was developed to enrich and detect aristolochic acids used in traditional Chinese medicine. A satisfactory recovery (92.7 - 97.5% for aristolochic acid Ⅰ and 92.6 - 99.4% for aristolochic acid Ⅱ) and an acceptable relative standard deviation (<4.0%) were obtained.


Assuntos
Adenina/química , Ácidos Aristolóquicos/isolamento & purificação , Fenômenos Magnéticos , Nanotubos de Carbono/química , Adsorção , Medicamentos de Ervas Chinesas/química , Compostos Férricos/síntese química , Compostos Férricos/química , Concentração de Íons de Hidrogênio , Cinética , Nanocompostos/química , Nanotubos de Carbono/ultraestrutura , Concentração Osmolar , Reprodutibilidade dos Testes , Dióxido de Silício/síntese química , Dióxido de Silício/química , Extração em Fase Sólida , Temperatura , Difração de Raios X
13.
Clin Interv Aging ; 15: 1343-1352, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848375

RESUMO

Objective: The aims of this study were to investigate the association between osteosarcopenic obesity (OSO) and physical performance in Chinese elderly communities. Methods: Our study population is comprised of residents of the Township Central Hospital in the suburban of Tianjin, China. Participants (n=303; percent body fat (PBF): ≥25% for men and ≥32% for women) were assessed using the direct segmental multi-frequency bioelectrical impedance analysis (BIA) for body composition. Sarcopenia was defined as the lower 20th percentile of appendicular skeletal muscle mass/height2 (ASMI). A quantitative ultrasound scan of each participants' calcaneus with a T score≤-1.0 was used to identify the prevalence of osteopenia/osteoporosis (OP). We divided people into four groups: obesity only (O), osteopenic obesity (OO), sarcopenic obesity (SO), and osteosarcopenic obesity (OSO). We assessed the physical performance by grip strength, 4-m walk test (WS) and timed up and go test (TUGT). Results: A total of 303 participants had completed data (89 men, 214 women; mean age of 68.8±6.0 years). The prevalence of OSO was 10.2% (men: 15.70%, women: 7.9%). After multiple adjustments, WS was significantly declined in OSO group when compared with the O group in men (mean value 95% CI was 0.84 (0.69, 0.99)) and women (mean value 95% CI was 0.93 (0.84, 1.02)). TUGT was significantly poorer in men (mean value 95% CI was 13.3 (10.6, 15.9)) and women (mean value 95% CI was 12.4 (11.2, 13.7)) with OSO when compared with the O group. Furthermore, the OSO group in women also had a significantly poorer TUGT compared with the OO group. The result of grip strength decreased significantly in women SO and OSO groups when compared with the O group (mean value 95% CI was 16.4 (14.5, 18.2) and 16.1 (13.9, 18.3)). But the results of grip strength in men showed no significant differences in any of the group. Conclusion: In Chinese community-dwelling elderly, slower WS and lower balance function were associated with OSO in men and women. Lower grip strength was associated with SO and OSO in women.

14.
Food Res Int ; 136: 109329, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32846528

RESUMO

Hong Qu glutinous rice wine (HQGRW) is produced from glutinous rice with the addition of the traditional fermentation starter Hong Qu (mainly Gutian Hong Qu and Wuyi Hong Qu) has been added. It is unpalatable and rejected by consumers because the bitter and umami tastes are too high. The objective of this study was to compare the dynamics of the microbial communities and amino acids especially those in the different traditional fermentation starters used during HQGRW fermentation, and elucidate the key microbes responsible for amino acids. Three widely-used types of Hong Qu starters were used which can make different bitterness and umami in our previous studies, namely, black Wuyi Hong Qu (WB), red Wuyi Hong Qu (WR), and Gutian Hong Qu (GT). The living dynamics of fungal and bacterial communities during the fermentation were determined by high-throughput sequencing and rRNA gene sequencing technology for the first time. The content of amino acids in the HQGRW were determined by reverse-phase high-performance liquid chromatography analysis. The results showed that there were differences between fungal communities during the fermentation process in Wuyi Hong Qu and Gutian Hong Qu starters and between bacterial communities during the fermentation process in the three types of starters. The amino acid content of the samples showed an increasing trend in each group. The total amino acids, as well as the bitter, sweet, umami, astringent amino acids, in the GT Hong Qu group increased more slowly during fermentation, as comparerd to those in WB and WR groups. Furthermore, Meyerozyma, Saccharomyces, Bacillus, Rhizopus, Pediococcus, Monascus, and Halomonas were strongly positively correlated with the content of bitter and umami amino acids (|r| > 0.6 with FDR adjusted P < 0.05) by Spearman's correlation analysis. To conclude, these findings may contribute to a better understanding of the bitter and umami amino acid production mechanism during traditional fermentation and helpful in improving the taste of HQGRW.

15.
J Int Med Res ; 48(8): 300060520943450, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32777962

RESUMO

OBJECTIVE: Osteoporosis can lead to bone fragility and an increased risk of bone fracture with resultant high morbidity and mortality. Living alone has been associated with various mental and physical health problems. However, the risk of osteoporosis among individuals with different living conditions and changing living conditions is unclear. We examined the risk of osteoporosis in different living conditions over a 3-year period in community-dwelling suburban elderly Chinese. METHODS: This study involved 288 elderly Chinese suburb-dwelling participants with no documented history of osteoporosis. All were aged ≥60 years (mean, 65.6±3.75 years; 157 men). A quantitative ultrasound scan of the calcaneus with a T score of <-2.5 was used to identify a high risk of osteoporosis. RESULTS: In total, 54.2% of participants were determined to have a high risk of osteoporosis (male, 51.6%; female, 57.3%). People who had always lived alone had a significantly higher risk of osteoporosis, even after adjusting for potential confounders. A change from living alone to living with others had no significant impact on the risk of osteoporosis. CONCLUSION: Our results indicate that living alone is associated with a high risk of osteoporosis. Thus, people who live alone may need regular bone tests to avoid adverse events.

16.
Cancer ; 126 Suppl 16: 3857-3866, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32710662

RESUMO

BACKGROUND: The role of postmastectomy radiotherapy (PMRT) in women with pT1-T2N1 breast cancer is controversial. The authors developed a nomogram that was predictive for overall survival (OS) and identified patients who derived no benefit from PMRT. METHODS: The authors retrospectively evaluated 4869 patients with pT1-T2N1 breast cancer who were treated with mastectomy between 2000 and 2014 in 11 Chinese hospitals. Rates of locoregional recurrence and distant metastasis were calculated using competing risk analysis, and disease-free survival and OS rates were calculated using the Kaplan-Meier method. Based on the risk factors identified from Cox regression analysis in 3298 unirradiated patients, a nomogram predicting OS was developed. The benefit of PMRT was evaluated in different risk groups stratified by the nomogram model. RESULTS: After a median follow-up of 65.9 months, the 5-year OS, disease-free survival, locoregional recurrence, and distant metastasis rates were 93.3%, 84.3%, 5.2%, and 8.3%, respectively. A total of 1571 patients (32.3%) underwent PMRT. On multivariable analyses, PMRT was found to increase OS significantly (hazard ratio, 0.61; P = .002). An OS prediction nomogram evaluated the effect of age; tumor location; tumor size; positive lymph node ratio; estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status; and treatment with trastuzumab. Based on nomogram scores, the entire patient cohort was classified into 3 risk groups. PMRT significantly improved the OS of patients in the intermediate-risk (P < .001) and high-risk groups (P = .004), but not in the low-risk group (P = .728). CONCLUSIONS: The authors developed a nomogram that is predictive of OS among women with pT1-T2N1 breast cancer after mastectomy. This nomogram may help to select a subgroup of patients with a good prognosis who will not benefit from PMRT.

17.
Respir Res ; 21(1): 192, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32689999

RESUMO

BACKGROUND: Severity of community-acquired pneumonia (CAP) depends on microbial pathogenicity, load and virulence, and immune responses. The Infectious Disease Society of America and the American Thoracic Society (IDSA/ATS) minor criteria responsible for clinical triage of patients with CAP are of unequal weight in predicting mortality. It is unclear whether the IDSA/ATS major/minor criteria might be strongly and positively associated with the immune responses. It is warranted to explore this intriguing hypothesis. METHODS: A prospective cohort study of 404 CAP patients was performed. Cold-inducible RNA-binding protein (CIRP) levels were measured using a sandwich-based enzyme-linked immunosorbent assay. The receiver operating characteristic curves were created and the areas under the curves were calculated to illustrate and compare the accuracy of the indices. RESULTS: Severe CAP patients meeting the major criteria had the highest plasma concentrations of CIRP. The more the number of most predictive minor criteria strongly associated to mortality, i.e. arterial oxygen pressure/fraction inspired oxygen ≤ 250 mmHg, confusion, and uremia, present, the higher the CIRP level. Interestingly, the patients with non-severe CAP meeting the most predictive minor criteria demonstrated unexpectedly higher CIRP level compared with the patients with severe CAP not fulfilling the criteria. Procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores, and mortality confirmed similar intriguing patterns. CIRP was strongly linked to PCT, IL-6, CRP, minor criteria, SOFA and PSI scores, and mortality (increased odds ratio 3.433). The pattern of sensitivity, specificity, positive predictive value, and Youden's index of CIRP ≥ 3.50 ng/mL for predicting mortality was the optimal. The area under the receiver operating characteristic curve of CIRP was the highest among the indices. CONCLUSIONS: CIRP levels were strongly correlated with the IDSA/ATS major/minor criteria. CIRP might determine the severity and the presences of major/minor criteria and best predicted mortality, and a CIRP of ≥ 3.50 ng/mL might be more valuable cut-off value for severe CAP, suggesting that CIRP might be a novel and intriguing biomarker for pneumonia to monitor host response and predict mortality, which might have implications for more accurate clinical triage decisions.

18.
Nanotechnology ; 31(49): 495708, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-32717727

RESUMO

The design of hierarchical heterogeneous structures with rational components is considered as a promising method to enhance the properties of electrocatalyst. Binary metal oxides, with high electrochemical activity, have attracted considerable interest in glucose determination. In this work, we synthesized the CuCo2O4@NiCo2O4 hybrid structure on conductive carbon cloth (CC) via a simple two-step hydrothermal process and investigated its catalytic ability toward glucose. The two individual components that make up this hybrid electrode have good electrical conductivity and excellent catalytic properties for glucose, so the smart combination of these two active materials can provide more catalytic sites and sufficient redox couples for the glucose oxidation. As a result, the CuCo2O4@NiCo2O4 modified CC presented superior glucose sensing properties, including ultrahigh sensitivity, fast response time, wide linear range and acceptable detection limit. Besides, the sample also exhibited good selectivity for substances in human blood that interfere with glucose detection, such as UA, AA, fructose, sucrose and KCl. The potential of the CuCo2O4@NiCo2O4/CC electrode for practical application was investigated by measuring the glucose concentration in real serum samples. These results prove that the construction of hierarchical ordered structure is conducive to the improvement of glucose sensor.

19.
J Hematol Oncol ; 13(1): 88, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620135

RESUMO

Due to acromegaly's insidious onset and slow progression, its diagnosis is usually delayed, thus causing severe complications and treatment difficulty. A convenient screening method is imperative. Based on our previous work, we herein developed a new automatic diagnosis and severity-classification model for acromegaly using facial photographs by deep learning on the data of 2148 photographs at different severity levels. Each photograph was given a score reflecting its severity (range 1~3). Our developed model achieved a prediction accuracy of 90.7% on the internal test dataset and outperformed the performance of ten junior internal medicine physicians (89.0%). The prospect of applying this model to real clinical practices is promising due to its potential health economic benefits.

20.
Toxicol Appl Pharmacol ; 406: 115137, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682830

RESUMO

Pyrrolizidine alkaloids (PAs) are a group of hepatic toxicant widely present in plants. Cytochrome P450 (CYP) 3A plays a key role in metabolic activation of PAs to generate electrophilic metabolites, which is the main cause of hepatotoxicity. We have previously demonstrated the sex difference in developmental toxicity and hepatotoxicity in fetal rats exposed to monocrotaline (MCT), a representative toxic PA. The aim of this study was to explore the underlying mechanism. 20 mg·kg-1·d-1 MCT was intragastrically given to pregnant Wistar rats from gestation day 9 to 20. CYP3As expression and pregnane X receptor (PXR) activation were specifically enhanced in female fetal liver. After MCT treatment, we also observed a significant increase of CYP3As expression in LO2 cells (high PXR level) or hPXR-transfected HepG2 cells (low PXR level). Employing hPXR and CYP3A4 dual-luciferase reporter gene assay, we confirmed the agonism effect of MCT on PXR-dependent transcriptional activity of CYP3A4. Agonism and antagonism of the androgen receptor (AR) either induced or blocked MCT-induced PXR activation, respectively. This study was the first report identifying that MCT served as PXR agonist to induce CYP3A expression. CYP3A induction may increase self-metabolic activation of MCT and subsequently lead to more severe hepatotoxicity in female fetus. While in male, during the intrauterine period, activated AR by testosterone secretion from developing testes represses MCT-induced PXR activation and CYP3A induction, which may partially protect male fetus from MCT-induced hepatotoxicity.

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