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1.
BMC Gastroenterol ; 20(1): 343, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059614

RESUMO

BACKGROUND: The significance of human epidermal growth factor receptor 2 (Her2) and nucleus-associated antigen Ki-67 expression remains controversial in gastric adenocarcinoma (GaC). The aim of this study was to investigate the expression and clinicopathologic and prognostic significance of Her2 and Ki-67 in resected GaC without distant metastasis. METHODS: Malignant tissues and clinicopathologic data were obtained from 195 patients with resected non-metastatic GaC. Immunohistochemistry staining was performed to examine the expression of Her2 and Ki-67; their association with clinicopathologic factors were investigated using logistic regression, and their association with survival was explored using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: Her2 was majorly expressed in cell membrane and Ki-67 in cell nucleus in non-metastatic GaC. Stronger Her2 expression was significantly associated with better tumor differentiation, neurovascular invasion, less advanced pathological tumor (pT) stage, and more advanced pathological node (pN) stage; while Ki-67 expression was not significantly associated with any investigated clinicopathologic factors. Patients with both negative Her2 and negative Ki-67 expression had poorer tumor differentiation, and more advanced pT and pathological tumor-node-metastasis (pTNM) stages; the association with pT and pTNM stages were further confirmed by multivariable analyses, especially in node-negative disease. Her2 or Ki-67 alone was not significantly associated with pTNM stage. A strongly positive (+++) Her2 expression was associated with poorer survival in multivariable analysis only (P = 0.047); while Ki-67 or combined expression was not significantly associated with prognosis. CONCLUSIONS: In non-metastatic GaC, Her2 expression and combined expression of Her2 and Ki-67 were associated with several clinicopathologic factors including tumor differentiation and stage, and only a +++ Her2 expression was associated with poorer prognosis in multivariable analysis with marginal significance in this study; while Ki-67 alone had both limited clinicopathologic and prognostic values.

2.
Trials ; 21(1): 844, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046128

RESUMO

BACKGROUND: Traditional Chinese medicine (TCM) has a long history of use in breast cancer, but lacking systematic evidence to support its clinical benefits. In this study, we evaluated the prophylactic and therapeutic effects of moxibustion combined with decoctions for treating chemotherapy-induced myelosuppression (CIM) in early-stage breast cancer patients. METHODS: This is a randomized controlled clinical trial single-blinded for TCM decoction but not moxibustion. Patients are equally divided into the control group without decoction and moxibustion treatment (control), the decoction+moxibustion group (MD), and the placebo+moxibustion group (MP), according to the following stratification factors: age (below 40s, 40s, 50s, and 60s or above), chemotherapy regimen (anthracyclines, taxanes, anthracyclines+taxane, and others), and chemotherapy strategy (adjuvant and neoadjuvant). The TCM decoction is Wenshen Shengbai Decoction. The anticipated sample size is 462 cases (154 cases in each group). All participants are expected to treat with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF). The primary outcomes include the proportion of patients with relief of leukopenia and/or neutropenia, the myelosuppression-associated serious adverse event including grade 3-4 leukopenia and/or neutropenia, and febrile neutropenia, and the dose of rhG-CSF. The secondary outcomes include chemotherapy adherence, stratified analysis, adverse reactions, quality of life by EORTC Breast-Cancer-Specific Quality of Life Questionnaire including EORTC QLQ-C30 (V3.0) and QLQ-BR23, TCM Constitution, and 3-year disease-free survival and overall survival. Baseline information including age, surgical approach, chemotherapy regimen and strategy, pathological stage, and molecular subtype will be recorded. DISCUSSION: This will be the first randomized controlled trial to evaluate the efficacy of moxibustion combined with TCM decoction in treating CIM in early-stage breast cancer patients, aiming to standardize the TCM decoction and moxibustion method, thus providing evidence for its clinical benefit. TRIAL REGISTRATION: chictr.org.cn ChiCTR-INR-16009557 . Registered on 23 October 2016.

3.
Front Immunol ; 11: 2133, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013900

RESUMO

The small GTPase Rab5 is one of the master regulators of vesicular trafficking that participates in early stages of the endocytic pathway, such as endocytosis and endosome maturation. Three Rab5 isoforms (a, b, and c) share high sequence identity, and exhibit complex functions. However, the role of Rab5c in virus infection and cellular immune responses remains poorly understood. In this study, based on the established virus-cell infection model, Singapore grouper iridovirus (SGIV)-infected grouper spleen (GS) cells, we investigated the role of Rab5c in virus infection and host immune responses. Rab5c was cloned from the orange-spotted grouper, Epinephelus coioides, and termed EcRab5c. EcRab5c encoded a 220-amino-acid polypeptide, showing 99% and 91% identity to Anabas testudineus, and Homo sapiens, respectively. Confocal imaging showed that EcRab5c localized as punctate structures in the cytoplasm. However, a constitutively active (CA) EcRab5c mutant led to enlarged vesicles, while a dominant negative (DN) EcRab5c mutant reduced vesicle structures. EcRab5c expression levels were significantly increased after SGIV infection. EcRab5c knockdown, or CA/DN EcRab5c overexpression significantly inhibited SGIV infection. Using single-particle imaging analysis, we further observed that EcRab5c disruption impaired crucial events at the early stage of SGIV infection, including virus binding, entry, and transport from early to late endosomes, at the single virus level. Furthermore, it is the first time to investigate that EcRab5c is required in autophagy. Equally, EcRab5c positively regulated interferon-related factors and pro-inflammatory cytokines. In summary, these data showed that EcRab5c exerted a bi-functional role on iridovirus infection and host immunity in fish, which furthers our understanding of virus and host immune interactions.

4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5733-5736, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019276

RESUMO

Populations around the world are rapidly ageing. Age-friendly environments address the significance of continuous inhome vital sign monitoring. Impulse Radio Ultra-WideBand (IR-UWB) radar serves as a household healthcare assistance, providing non-contact vital sign monitoring without privacy issues and illumination limitation. However, the body movements bring difficulty in extracting heartbeat from radar signals, let alone obtaining complete information with body occlusions among multiple targets. This paper proposes a Multiple Moving Targets Heartbeat Estimation And Recovery (MMT-HEAR) approach to extract vital signs using IR-UWB radars. CLEAN and Joint Probability Data Association (JPDA) algorithms are firstly performed on each radar to estimate target-to-antenna distances of multiple targets. Considering signal obstruction and attenuation for targets occluded by others, the location-based distance optimization is proposed to refine these distances by combining information from all radars. Then the mapping from signal amplitudes to refined distances is introduced and combined with the Variational Nonlinear Chirp Mode Decomposition (VNCMD) to extract vital signs with body movements. To the best of our knowledge, this is the first attempt to monitor vital signs of multiple moving targets with radars. The averaging accuracy for two moving targets heartbeat monitoring during a 20-minutes observation is 85.93% with MMT-HEAR. Compared to two other conventional methods, the MMT-HEAR approach yields improvements of 16.11% and 10.16%, revealing the efficiency and robustness of this proposed approach.

5.
Mol Genet Genomic Med ; : e1524, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030252

RESUMO

BACKGROUND: Skeletal ciliopathies are a group of clinically and genetically heterogeneous disorders with the spectrum of severity spanning from relatively mild to prenatally lethal. The aim of our study was to identify pathogenic mutations in a Chinese family with two siblings presenting a Short-rib polydactyly syndrome (SRPS)-like phenotype. METHOD: Karyotyping and NGS-based CNVseq were performed. Obtaining the negative results in karyotyping and CNVseq, whole-exome sequencing (WES) using genomic DNA (gDNA) extracted from the umbilical cord blood of the first fetus was carried out, followed by bioinformation analysis. The candidate pathogenic variants were confirmed by Sanger sequencing in the family. RESULTS: No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the affected fetus with SRPS-like phenotype. WES analysis identified two novel compound heterozygous variants in DYNC2LI1, c.358G>T (p.Pro120Ser; NM_001193464), and c.928A>T (p.Lys310Ter; NM_ 001193464). Bioinformatics analysis suggested that c.358G>T (p.Pro120Ser) was likely pathogenic and c.928A>T (p.Lys310Ter) was pathogenic. Sanger sequencing of the two variants in family reveal that c.358G>T was from paternal origin and c.928A>T was from maternal origin, and the second affected fetus had the same compound heterozygous variants in DYNC2LI1. Definitive diagnosis of short-rib thoracic dysplasia 15 with polydactyly (SRTD15) was made in the family. CONCLUSION: Our results expand the mutational spectrum of DYNC2LI1 in severe skeletal ciliopathies. WES facilitates the accurate prenatal diagnosis of fetal skeletal ciliopathy, and provides helpful information for genetic counseling.

6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 485-488, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018033

RESUMO

Utilizing Impulse Radio Ultra-WideBand (IR-UWB) radar for vital sign monitoring has attracted growing interest due to the noncontact measurement without privacy concerns. Most of existing researches assume that the subject's chest is directed to the radar antenna, to ensure the strength of backscattered signals from chest movement. However, a large angle between the antenna and the subject's chest caused by the body orientation badly affects the monitoring accuracy. Multiple observations of the same cardiopulmonary activity from different orientations provide more available measurements. This paper addresses the challenge by using an IR-UWB radar network instead of a single radar. Three IR-UWB radars are placed as endpoints of an equilateral triangle to collect vital sign information of a subject sitting at the center. A Conditional Generative Adversarial Network (CGAN) method is proposed to fuse multisensory data. First, the body orientation is classified by combining signal features and a random forest classifier. Then the impact of different angles on vital sign monitoring results is discussed and validated in each orientation. The data fusion process is modelled as an extended generative network with orientation based condition to produce the enhanced vital signal. This signal is optimized with the discriminator network to a fitted sinusoidal wave with heartbeat and respiratory information. Experimental results on measuring Heartbeat Rate (HR) in different orientations reveal the effectiveness and stability of the proposed method.


Assuntos
Radar , Processamento de Sinais Assistido por Computador , Coração , Frequência Cardíaca , Respiração
7.
Medicine (Baltimore) ; 99(40): e22315, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019407

RESUMO

INTRODUCTION: chronic obstructive pulmonary disease (COPD) is 1 of the leading causes of morbidity and mortality worldwide; its economic and social burdens are substantial and increasing. Recent years, an increasing number of study has shown the promising advantage of Erchen decoction (ECD) combined with sanziyangqin decoction (SZYQD) in treating COPD. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to provide a protocol for a systematic review on ECD combined with SZYQD for COPD and provide effective evidence for further clinical use. METHODS AND ANALYSIS: We will conduct a Computerized literature searches in the following databases: PubMed, MEDLINE, EMBASE, Cochrane Library, China national information network, China biomedical literature database (CBM), Chinese Scientific Journals Database and wanfang database, from their inception to June 2020, without restrictions of language. Study selection, data collection, and evaluation of the quality of evidence will be performed by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: This study will systematically evaluate the effectiveness and safety of ECD combined with SZYQD for COPD. The results will be published in a peer-reviewed journal. CONCLUSION: This study will provide evidence from the current published RCTs of whether ERD combined with SZYQD is an effective and safe intervention for COPD. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence. In this study, no individual data from participants will be involved, so ethics approval is not required. OPEN SCIENCE FRAMEWORK(OSF)REGISTRATION NUMBER: August 19, 2020; osf.io/zxm24.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Testes de Função Respiratória
8.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33097539

RESUMO

Leveraging the endogenous homology-directed repair (HDR) pathway, the CRISPR-Cas9 gene-editing system can be applied to knock in a therapeutic gene at a designated site in the genome, offering a general therapeutic solution for treating genetic diseases such as hemoglobinopathies. Here, a combined supramolecular nanoparticle (SMNP)/supramolecular nanosubstrate-mediated delivery (SNSMD) strategy is used to facilitate CRISPR-Cas9 knockin of the hemoglobin beta (HBB) gene into the adeno-associated virus integration site 1 (AAVS1) safe-harbor site of an engineered K562 3.21 cell line harboring the sickle cell disease mutation. Through stepwise treatments of the two SMNP vectors encapsulating a Cas9•single-guide RNA (sgRNA) complex and an HBB/green fluorescent protein (GFP)-encoding plasmid, CRISPR-Cas9 knockin was successfully achieved via HDR. Last, the HBB/GFP-knockin K562 3.21 cells were introduced into mice via intraperitoneal injection to show their in vivo proliferative potential. This proof-of-concept demonstration paves the way for general gene therapeutic solutions for treating hemoglobinopathies.

9.
J Clin Lab Anal ; : e23582, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32951212

RESUMO

BACKGROUND: Trisomy of the short arm of chromosome 17 is a rare genomic disorder. The clinical features of complete trisomy 17p syndrome have been described. Most cases of this syndrome have been found in infants and children, but only a few cases were found by ultrasound in the prenatal period. METHODS: We report a case of complete trisomy 17p syndrome, which was inherited from paternal balanced translocation t(15;17)(q11.2;q11.2). A pregnant woman underwent an ultrasound examination at 24 weeks of gestation. Amniotic fluid was collected by amniocentesis. Cytogenetic and single nucleotide polymorphism array analyses were performed. We further reviewed the relationship between duplication regions and the clinical phenotype. RESULTS: Ultrasonographic evaluation showed intrauterine growth retardation and a right choroid plexus cyst, but the gallbladder was not observed. The fetal karyotype was 46,XX,der(17)t(15;17)(q11.2;q11.2)pat. The father's karyotype was 46,XY,t(15;17)(q11.2;q11.2). The single nucleotide polymorphism array results showed arr[GRCh37] 17p13.3q11.1(525-25309337)×3, which indicated a 25.309-Mb duplication. CONCLUSION: Complete trisomy 17p syndrome shows severe malformations. Intrauterine growth retardation is the most typical manifestation of this syndrome as shown by ultrasonography in the second trimester of pregnancy. The genotype-phenotype relationships of complete trisomy 17p syndrome are not completely consistent. To further determine these relationships, additional cases are necessary to provide more information from ultrasonographic findings during pregnancy.

10.
Postgrad Med ; : 1-9, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990128

RESUMO

OBJECTIVES: To evaluate the performance and cost-effectiveness of existing diabetes risk scores (DRSs) to screen for undiagnosed diabetes mellitus (UDM) and prediabetes (PD) in a community-based southwestern Chinese population. METHODS: Participants in TIDE-Chengdu survey with requisite data and without known diabetes were included. Five Chinese-derived DRSs and six non-Chinese-derived DRSs were included for evaluation. Their performance in detecting UDM and UMD or PD (UDM/PD) was assessed using the C-statistic. The cost-effectiveness of the optimal DRS was compared with that of capillary fasting blood glucose (CFBG). RESULTS: Of the 1,692 TIDE-Chengdu survey participants included, 177 (10.5%) had UDM and 339 (20.0%) had PD. The rural participants (N = 737) were more likely to have UDM (13.4% vs. 8.2%) and PD (24.8% vs. 16.3%) than their urban counterparts (N = 955) (P < 0.0001). In the full population, the included DRSs all showed good discrimination in detecting UDM (C-statistic: 0.699 to 0.762) and UDM/PD (C-statistic: 0.717 to 0.769), but the New Chinese DRS (NCDRS) performed best for both UDM and UDM/PD. The DRSs evaluated all showed better performance in urban participants than rural participants for both UDM (C-statistic: 0.718 to 0.795 vs. 0.642 to 0.720) and UDM/PD (C-statistic: 0.729 to 0.793 vs. 0.682 to 0.726) (all P < 0.05). The mean cost per UDM/PD case identified was lower with NCDRS at score 25 (¥503.3($71.9)) and 27 (¥490.5 ($70.1)) than CFBG at 5.0, 5.1, 5.2, or 5.3 mmol/L (¥631.7 ($90.2), ¥611.8 ($87.4), ¥579.2 ($82.7) and ¥551.9 ($78.8)), whereas the mean costs per UDM case identified was higher with NCDRS at score 25 (¥1379.3 ($197.0)) and 27 (¥1315.1 ($187.9)) than CFBG at 5.3, 5.4, or 5.5 mmol/L (¥1301.7 ($186.0), ¥1247.7 ($178.2) and ¥1173.3 ($167.6)). CONCLUSION: The NCDRS represents a valid and cost-effective tool for use in southwestern China to identify high-risk patients with UDM or PD who need a diagnostic test.

11.
Nanotechnology ; 31(48): 485207, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32931471

RESUMO

1D ZnO nanostructures have been widely explored due to their potential applications in ultraviolet (UV) region photodetectors because of their unique structural and optoelectronic properties. However, a large number of surface defect states leading to a noticeable dark current hinders their practical applications in UV photodetection. In this work, we have shown improved ZnO/Al2O3 core-shell microrod photodetectors, whose performance is significantly enhanced by defect passivation and the introduction of trap states by atomic layer deposition grown thin amorphous Al2O3 shell layer, as evidenced by steady-state and transient photoluminescence investigations. The photodetectors demonstrated suppressed dark current and increased photocurrent after capping the Al2O3 layer. Specifically, the ZnO/Al2O3 core-shell microrod photodetector exhibited a photoresponsivity as high as 0.019 A/(W cm-2) with the dark current as low as ∼1 × 10-11 A, and a high I light/I dark ratio of ∼104 under relatively weak light illumination (∼10 µW cm-2). The results presented in this work provide valuable pathways to boost the performance of 1D ZnO microrod-based photodetectors for future practical applications.

12.
Medicine (Baltimore) ; 99(38): e22066, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957328

RESUMO

INTRODUCTION: Type 2 diabetes mellitus(T2DM) is a widespread attention of the world's major health problems. The international diabetes federation (IDF) has released the "global overview of diabetes (ninth edition)". By 2019. It can lead to complications and even death. Among them, the use of Rhizoma Coptidis (Huanglian) at large dose has also been proved to be effective in clinical practice. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to carry out systematic evaluation on coptis coptis and provide effective evidence for further research. METHODS AND ANALYSIS: We will search the following electronic databases from their inception to May 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure. Primary outcomes:fasting blood glucose and glycosylated haemoglobin (A1c). SECONDARY OUTCOMES: plasma insulin,blood lipid profile,adverse events,and cost associated with the intervention and hospital visit. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the effectiveness and safety of large dose of Huanglian intervention for people with T2DM. CONCLUSION: The systematic review of this study will summarize the current published evidence of large dose of Huanglian for the treatment of T2DM, which can further guide the promotion and application of it. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations.Open Science Framework(OSF)registration number: July 21, 2020. https://osf.io/w7bj6.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Projetos de Pesquisa , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Ann Palliat Med ; 9(5): 3313-3325, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921127

RESUMO

BACKGROUND: The aim of the present study was to investigate the risk factors for in-hospital mortality among patients with type 2 diabetes mellitus (T2DM) and concomitant community-acquired pneumonia (CAP) and establish a risk prediction score. METHODS: Data from 1,360 adult patients with T2DM and concomitant CAP hospitalized in two grade 3A hospitals between 2009 and 2019 were collected through electronic medical records. Data obtained included the status of diabetes mellitus, comorbidities, laboratory and imaging findings, and treatment outcomes. Statistical analysis was conducted to investigate the risk factors affecting prognosis, and a clinical risk prediction score was designed. RESULTS: Based on the patients' treatment outcomes (deceased, improved and cured), the cohort was divided into two groups: deceased and improved; 16 parameters were significant after segmentation. However, the following nine parameters were independent predictors of mortality: neutrophil-lymphocyte ratio (NLR) ≥4, pulse rate ≥125 bpm, change in state of consciousness, arterial blood pH ≤7.35, age ≥65 years, serum sodium ≤130 mmol/L, initial fasting blood glucose ≥9 mmol/L, multilobar involvement, and diabetic nephropathy. Based on these findings, a risk prediction score was established, and bootstrap validation was performed. The risk prediction score was significantly superior to CURB-65 [confusion, urea >7 mmol/L, respiratory rate >30/min, low blood pressure (systolic <90 mmHg or diastolic <60 mmHg), age >65 years] and slightly superior than the pneumonia severity index (PSI). CONCLUSIONS: The influencing factors for in-hospital mortality among patients with T2DM and concomitant CAP included advanced age, change in state of consciousness, increased pulse rate, acidosis, high NLR, high platelet-lymphocyte ratio, hyponatremia, hyperglycemia, and diabetic nephropathy. These parameters should be recognized in clinical practice, with active interventions to improve the treatment success rate. The risk prediction score effectively differentiated the mortality risk of inpatients, thereby providing guidance on clinical decision-making.

14.
Chem Biol Drug Des ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32946197

RESUMO

Andrographolide is a traditional Chinese medicine monomer with many pharmacological activities, but has potential nephrotoxicity. Here, we aim to investigate the relationship between modification of andrographolide structure and its nephrotoxicity. Twenty-three andrographolide derivatives were synthesized, and their structures were confirmed by 1 H-NMR and HRMS. Nephrotoxicity of these compounds against human renal tubular epithelial (HK-2) cells was evaluated using the MTT assay. The results indicated that most of them had significantly reduced nephrotoxicity, especially compounds III, V, and IXc , with IC50 values of 1,985, 1,300, and 806.9 µmol/L, respectively, which were obviously superior to andrographolide (IC50 30.60 µmol/L). However, compounds Ia -If (IC50 values < 30 µmol/L), the 14-OH derivatives of andrographolide, showed higher nephrotoxicity than that of andrographolide. Three-dimensional quantitative structure-activity relationship (3D-QSAR) models of COMFA and COMSIA were established (COMFA: q2  = 0.639, r2  = 0.951; COMSIA: q2  = 0.569, r2  = 0.857). This model allowed proposing five new compounds with lower theoretical nephrotoxicity, which would be worthwhile to synthesize and evaluate. We believe that predicted models will help us to understand the structural modification requirements of andrographolide to reduce the nephrotoxicity, and further investigations will be needed to determine the mechanism involved in the effect of less nephrotoxic compounds.

15.
Nat Commun ; 11(1): 4489, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895384

RESUMO

We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Vesículas Extracelulares/genética , Neoplasias Hepáticas/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Química Click/instrumentação , Química Click/métodos , Química Computacional , Simulação por Computador , Diagnóstico Diferencial , Dimetilpolisiloxanos/química , Progressão da Doença , Detecção Precoce de Câncer/instrumentação , Feminino , Células Hep G2 , Humanos , Dispositivos Lab-On-A-Chip , Biópsia Líquida/instrumentação , Biópsia Líquida/métodos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pessoa de Meia-Idade , Nanoestruturas/química , Nanofios/química , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa/instrumentação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
16.
Mol Cell Endocrinol ; 518: 111037, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32966862

RESUMO

Ubiquitin-specific protease 7 (USP7/HAUSP) is known to regulate multiple cellular phenomena, including cell cycle progression and proliferation, and is involved in binding and stabilizing specific target proteins through deubiquitylation. However, the detailed role of USP7 in papillary thyroid carcinoma (PTC) remains to be investigated. In this study, our results showed that USP7 was upregulated in PTC tissues compared with adjacent nontumour tissues. Consistently, a series of gain/loss functional assays in vivo and in vitro demonstrated the role of USP7 in promoting PTC cell proliferation. Furthermore, we showed that there was a negative correlation between USP7 and the CDK inhibitor p57KIP2 expression in PTC tissues and that USP7 facilitated PTC cell proliferation by inhibiting p57KIP2. Mechanistically, USP7 inhibited p57KIP2 expression by modulating TBX3, directly binding to TBX3, and decreasing its ubiquitination and degradation. Our findings demonstrated that USP7 played a critical oncogenic role in PTC tumorigenesis, suggesting that USP7 might act as a prognostic and therapeutic target for PTC progression.

17.
Surgery ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32948335

RESUMO

BACKGROUND: Why certain patients after total thyroidectomy for thyroid cancer who do not have distant metastasis have increased serum stimulated thyroglobulin (s-Tg) is unknown. The aim of our study was to systematically investigate the associations of preablation s-Tg with clinical and tumor characteristics in children and young adults less than 20 years old after total thyroidectomy for papillary thyroid cancer. METHODS: We performed a retrospective analysis of 93 children and young adults younger than 20 years old who had undergone total thyroidectomy and were without known distant metastases who underwent remnant ablation. Before any remnant preablation, we assessed the association of s-Tg after thyroid hormone withdrawal with the clinical and histopathologic characteristics according to the American Thyroid Association pediatric initial risk classification system. RESULTS: The median age was 18 years, and the majority of patients were female (80%). The preablation s-Tg ranged from 0.02 to 902.00 ng/mL, with a median of 9.2 ng/mL. Forty-five (48%) patients had an increased preablation s-Tg >10 ng/mL. In multivariate analyses of clinical and tumor characteristics, high-risk stratification and high neck uptake (>2%) were the independent predictive factors for the presence of an increased preablation s-Tg. CONCLUSION: Children and young adults younger than 20 years old with high-risk stratification and high neck uptake are likely to present a high level of preablation s-Tg after total thyroidectomy for papillary thyroid cancer. Continued long-term surveillance is necessary in this cohort of patients to confirm the role of preablation s-Tg as a biomarker for monitoring postoperative residual disease.

18.
Cancer Res ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948605

RESUMO

The IL-2 receptor (IL-2R) is an attractive cancer immunotherapy target that controls immunosuppressive T regulatory cells (Tregs) and anti-tumor T cells. Here we used IL-2Rß-selective IL-2/anti-IL-2 complexes (IL-2c) to stimulate effector T cells preferentially in the orthotopic mouse ID8agg ovarian cancer (OC) model. Despite strong tumor rejection, IL-2c unexpectedly lowered the tumor microenvironmental CD8+/Treg ratio. IL-2c reduced tumor microenvironmental Treg suppression and induced a fragile Treg phenotype, helping explain improved efficacy despite numerically increased Tregs without affecting Treg in draining lymph nodes. IL-2c also reduced Treg-mediated, high-affinity IL-2R signaling needed for optimal Treg functions, a likely mechanism for reduced Treg suppression. Effector T cell IL-2R signaling was simultaneously improved, suggesting that IL-2c inhibits Treg functions without hindering effector T cells, a limitation of most Treg depletion agents. Anti-PD-L1 antibody did not treat ID8agg, but adding IL-2c generated complete tumor regressions and protective immune memory not achieved by either monotherapy. Similar anti-PD-L1 augmentation of IL-2c and degradation of Treg functions were seen in subcutaneous B16 melanoma. Thus, IL-2c is a multifunctional immunotherapy agent that stimulates immunity, reduces immunosuppression in a site-specific manner, and combines with other immunotherapies to treat distinct tumors in distinct anatomic compartments.

19.
Medicine (Baltimore) ; 99(37): e22234, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925801

RESUMO

INTRODUCTION: Dry eye disease (DED) is one of the most prevalent ocular diseases which remains widely underestimated. New lifestyles driven by information technology and the rapid ageing process have brought DED a severe public health concern. And DED is highly related to the reduction in vision-related quality of life and interfere with daily activities. Since advanced age has been suggested as an important risk factor for DED, the aim of our study was to obtain the pooled prevalence of DED in the elderly over 60 years of age. METHODS AND ANALYSIS: The following databases will be searched from their inception to August 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WangFang, VIP medicine information, and China National Knowledge Infrastructure (CNKI). Primary outcomes: the number of participants and DED cases. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the prevalence of DED in the elderly population over 60 years of age. CONCLUSION: The systematic review of this study will summarize the current published evidence of epidemiological investigations of DED with advanced age classification. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OPEN SCIENCE FRA NETWORK (OSF) REGISTRATION NUMBER: August 12, 2020. osf.io/3jyb4. (https://osf.io/3jyb4).


Assuntos
Síndromes do Olho Seco/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Projetos de Pesquisa , Fatores de Risco
20.
Onco Targets Ther ; 13: 7295-7304, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801756

RESUMO

Objective: The Warburg effect, also known as aerobic glycolysis, plays a dominant role in the development of gastrointestinal (GI) cancers. In this study, we analyzed the expression of key genes involved in the Warburg effect in GI cancers and investigated the effect of suppressing the Warburg effect in vitro in liver cancer cell lines. Methods: The Cancer Genome Atlas (TCGA) RNA-Seq data were used to determine gene expression levels, which were analyzed with GraphPad Prism 7.00. Genetic alterations were queried with cBioPortal. The influence of the Warburg effect on liver cancer cell viability, migration and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity was determined by means of MTT, transwell and GAPDH activity assays. Results: The levels of expression of genes associated with the Warburg effect were increased in tumors. To our knowledge, this is the first report of upregulated expression of CUEDC2, HMGB2, PFKFB4, PFKP and SIX1 in liver cancer. Clinically, overexpression of these genes was associated with significantly worse overall survival of liver cancer patients. In vitro, selective inhibition of GADPH suppressed the growth and metastasis of Huh-7, Bel7404 and Hep3B hepatocellular carcinoma cell lines. Conclusion: The Warburg effect may play an important role in GI cancers, especially in liver cancer.

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