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1.
Neuroendocrinology ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31655821

RESUMO

BACKGROUND: Neuroendocrine tumor (NET) rarely occurs in the mediastinum and the etiology and pathogenesis are still unclear. OBJECTIVES: This study assessed inherited or de novo mutations in familial mediastinal NETs. METHOD: DNA samples from four persons were subjected to the whole-exome sequencing, and Sanger sequencing was used to identify Deleted in malignant brain tumor 1 (DMBT1) mutations in all 45 family members. RESULTS: All patients showed a germline DMBT1 mutation at 4971C. Sanger sequencing data showed that four NETs and two carriers in the first patient family had this DMBT1 mutation, and two NETs and four carriers in the second patient family had this DMBT1 mutation. The in vitro data showed that ectopic expression of DMBT1 reduced tumor cell viability and migration by arresting the G1/S phase of cell cycle. CONCLUSIONS: The data from current study identified a germline missense mutation in DMBT1D1657E as a susceptibility gene for familial mediastinal NETs.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1592-1595, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607317

RESUMO

OBJECTIVE: To investigate the gene-carrying rate and genetic types of thalassemia among the couples of child-bearing age in Ding'an, Hainan province. METHODS: A total of 1742 couples at child bearing age in the region were screened for thalassemia by detecting the mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV). If the sample data of either spouse of couples was tested as MCV<82 fl and /or MCH<27 pg, both samples of the couple would be further assayed by hemoglobin electrophoresis. Those samples of HbA2 2.5 % or HbA2>3.5 % were judged as positive in the preliminary screening, then subjected to genetic diagnosis of thalassemia. RESULTS: 478 cases out of 1 742 couples of child bearing age were diagnosed as thalassemia gene mutation, and the gene-carrying rate was 13.72 %. In those carriers, 42 couples were diagnosed with the same type of thalassemia, accounting for 3.67 %. The gene-carrying rate of α-thalassemia, ß-thalassemia and αß-thalassemia was 9.56%, 3.10% and 1.06 % respectively. CONCLUSION: The Ding'an area in Hainan Province is an area with high incidence of thalassemia, and the main genotype is α-thalassemia, showing a distribution of local characteristics. The government should make efferts to popularise the screening for thalassemia, so as to effectively prevent the birth of children with thalassemia major.

3.
Pest Manag Sci ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31605411

RESUMO

BACKGROUND: Baculoviruses provide long-lasting control of crop pests and are harmless to humans and non-target animals, making them attractive bioinsecticides. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has a wide-host range and is one such commercial bioinsecticide, but its low infectivity to older larvae and less-sensitive species precludes its large-scale application. We sought to improve the infectivity of AcMNPV. RESULTS: Two enhancing factors, the truncated enhancin from Agrotis segetum granulovirus and GP37 from Cydia pomonella granulovirus, were expressed in fusion with the N-terminal and middle domain of the polyhedrin envelope protein of AcMNPV. Western blotting and immunoelectron microscopy analysis indicated that the enhancing factors were expressed on the occlusion bodies of the resulting AcMNPV variants. Bioassays showed that the median lethal doses of the recombinant viruses were 3.9-fold to 7.4-fold lower than those of the wild-type virus against the second and fourth instar of Spodoptera exigua larvae. The yields of occlusion bodies from the two recombinants in S. exigua larvae were comparable with those of the wild-type virus both in vitro and in vivo. Further bioassays showed that the AcMNPV variants fusing the enhancing factors were incapable of infecting the second instar larvae of S. litura, Helicoverpa armigera, and Pyrausta nubilalis, which were not sensitive to the wild-type AcMNPV. CONCLUSION: These genetically modified AcMNPV variants exhibited an enhanced infectivity and may offer better baculovirus control of crop pests. This article is protected by copyright. All rights reserved.

4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 350-356, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31631602

RESUMO

Objective: To investigate the influence of continuous low-volume ventilation in cardiopulmonary bypass (CPB) on the expression of krebs von den lungen-6 (KL-6) and perioperative pulmonary function in adults undergoing valve surgery. Methods: From 2017 Sept. to 2018 Jan., 60 patients who received valve replacement surgery were prospectively comprised in this study. We randomly allocated these patients into control group ( n=30, non-ventilation) and experimental group ( n=30, continuous low-volume ventilation during CPB). At different perioperative time points, we identified the dynamic changes of pulmonary function and biomarkers which expressed in serum and bronchoalveolar lavage fluid (BALF). Meanwhile, we also compared perioperative clinical outcomes of the two groups. Results: The expression of serum KL-6 and BALF KL-6 in the two groups were both statistically significant( P<0.05). The oxygenation index increased with time and reached to the top point at T 1, then subsequently decreased with time ( P<0.05). The alveolar-arterial oxygen tension difference (P A-aO 2) in the two groups fluctuate with time, the differences have no statistical significance. According to linear correlation, the serum KL-6 level was negatively correlated with oxygenation indexes ( r=-0.525, P=0.003), while it was positively correlated with P A-aO 2 ( r=0.489, P=0.006). There were no significant differences between the two groups in clinical outcomes. Conclusion: Continuing low-volume ventilation during CPB could decrease the expression level of KL-6, while it has no significant influence on perioperative outcomes.

5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 357-361, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31631603

RESUMO

Objectives: To assess morphological changes of distal aorta and the risk factors for adverse aortic remodeling inpost-TEVAR(thoracic endovascular aortic repair) patients with acute Stanford B aortic dissection. Methods: We retrospectively investigated the patients who underwent TEVAR for a type B dissection between October 2005 and December 2015. CT angiogram (CTA) was obtained for each patients preoperatively, postoperatively and during the post-operational follow-up. Based on Criadol partition principle, we divided the aorta into descending thoracic aorta area, suprarenal abdominal aorta area, infrarenal abdominal aorta area and iliac artery area, and evaluated the distribution of aortic tears and the form of true and false lumen in different aortic partition. Univariate and multivariate logistic regression analyses were used to analyze the risk factors affecting distal aortic remodeling. Results: Of 216 patients (mean follow-up (3.9±2.1) years) who were regularly followed up in our center, 47 patients (21.8%) occurred adverse remodeling in distal aorta. Univariate logistic regression indicated that abnormal aortic wall structure (Marfan's syndrome) and patent false lumen (existence of distal tears, decreased complete false lumen thrombosis) were associated with distal aortic adverse remodeling. Multivariate logistic regression showed that more tears in descending thoracic aorta area ( OR=1.36, 95% CI=1.12-1.58, P=0.005) and less tears in infrarenal abdominal aorta area ( OR=0.49, 95% CI=0.22-0.71, P<0.001) were independent risk factors affecting remodeling in distal aorta after TEVAR. Conclusions: Aortic wall structure abnormalities, a patent false lumen, more tears in descending thoracic aorta area, less tears in infrarenal abdominal aorta area are independent risk factors for adverse aortic remodeling in post-TEVAR patients with acute Stanford B aortic dissection.

6.
Medicine (Baltimore) ; 98(38): e17141, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567953

RESUMO

The aim of this study was to evaluate the application of transthoracic echocardiography for the diagnosis of infective endocarditis (IE) to provide a basis for the better treatment of IE. From October 2016 to October 2018, 87 consecutive patients with IE at our hospital were selected for this study. All the patients were subjected to transthoracic echocardiography. The morphology, structure, activity, and closure of the patients' heart valves were observed for vegetation identification, and the size, number, location, morphology, and echo intensity of vegetation, as well as degree of valve involvement, were determined.The 87 patients investigated in this study included 38 cases of congenital heart disease, 27 cases of nonrheumatic valvular heart disease, 12 patients who underwent valve surgery, 5 cases of rheumatic valvular heart disease, and 5 patients with no obvious signs of heart disease. The most common clinical manifestations were heart murmur in 80 cases and fever in 60 cases. The most common complications were heart failure in 35 cases, followed by organ embolism in 12 cases. There were 36 cases of positive blood cultures, including 26 cases of Gram-positive cocci and 10 cases of Gram-negative bacilli. Echocardiography showed aortic valve involvement in 37 cases, mitral valve involvement in 34 cases, tricuspid valve involvement in 10 cases, pulmonary valve involvement in 2 cases, and the involvement of an artificial valve in 5 cases. Twenty-six of these cases showed multiple valve involvement, and 20 patients exhibited serious complications. No significant differences were found between echocardiography and actual surgical observations with respect to their accuracy in detecting the size, number, and location of vegetation in the 69 patients who underwent surgery (P > .05). Echocardiography could detect the occurrence of severe complications, namely, the rupture of chordae tendineae, valve prolapse, valve perforation, and paravalvular abscess, and no significant difference in diagnostic accuracy was found between echocardiography and surgical observations (P > .05).Transthoracic echocardiography can rapidly and accurately detect IE vegetation and its complications and has important clinical value for guiding clinical treatment and determining prognosis.


Assuntos
Endocardite/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Ecocardiografia , Endocardite/diagnóstico , Endocardite/patologia , Feminino , Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Adulto Jovem
7.
Environ Pollut ; 255(Pt 2): 113329, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31600704

RESUMO

Transcription factors including pregnane X receptor (Pxr) and nuclear factor-erythroid 2-related factor-2 (Nrf2) are important modulators of Adenosine triphosphate-binding cassette (ABC) transporters in mammalian cells. However, whether such modulation is conserved in zebrafish embryos remains largely unknown. In this manuscript, pxr- and nrf2-deficient models were constructed with CRISPR/Cas9 system, to evaluate the individual function of Pxr and Nrf2 in the regulation of ABC transporters and detoxification of heavy metal ions like Cd2+ and Ag+. As a result, both Cd2+ and Ag+ conferred extensive interactions with ABC transporters in wild type (WT) embryos: their accumulation and toxicity were affected by the activity of ABC transporters, and they significantly induced the mRNA expressions of ABC transporters. These induction effects were reduced by the mutation of pxr and nrf2, but elevations in the basal expression of ABC transporters compensated for the loss of their inducibility. This could be an explanation for remaining transporter function in both mutant models as well as the unaltered toxicity of metal ions in pxr-deficient embryos. However, mutation of nrf2 disrupted the production of glutathione (GSH), resulting in the enhanced toxicity of Cd2+/Ag+ in zebrafish embryos. In addition, elevated expressions of other transcription factors like aryl hydrocarbon receptor (ahr) 1b, peroxisome proliferator-activated receptor (ppar)-ß, and nrf2 were found in pxr-deficient models without any treatment, while enhanced induction of ahr1b, ppar-ß and pxr could only be seen in nrf2-deficient embryos after the treatment of metal ions, indicating different compensation phenomena for the absence of transcription factors. After all, pxr-deficient and nrf2-deficient zebrafish embryos are useful tools in the functional investigation of Pxr and Nrf2 in the early life stages of aquatic organisms. However, the compensatory mechanisms should be taken into consideration when interpreting the results and need in-depth investigations.

8.
Exp Cell Res ; 385(1): 111644, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614132

RESUMO

Human anterior gradient-2 (AGR2), a member of protein disulfide isomerase (PDI) family, is upregulated in various human cancers and reportedly has oncogenic activities. However, the functional roles of AGR2 and its regulation in colorectal cancer (CRC) remain unclear. Here, we showed that AGR2 promoted CRC tumorigenesis and progression in vitro and in vivo and acted as an independent prognostic factor of poor outcome. AGR2 was negatively regulated by DNA methyltransferase 3a (DNMT3a) through directly methylating AGR2 promoter and by a DNMT3a-SPRY2-miR-194 axis. Moreover, AGR2 mediated the resistance to 5-Aza-2'-deoxycytidine (5-Aza) treatment. Knockdown of AGR2 improved the therapeutic effect of 5-Aza in human CRC xenograft tumor model. Thus, our work supports AGR2's oncogenic role in CRC, reveals DNMT3a-mediated epigenetic modulation on AGR2 promoter, and uncovers a new DNMT3a signaling module controlling expression of AGR2. Upregulated AGR2 offset 5-Aza mediated epigenetic therapy. This work might provide potential targets for clinical anti-cancer therapy.

9.
Org Lett ; 21(21): 8582-8586, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618034

RESUMO

A chiral N-heterocyclic-carbene-catalyzed cascade asymmetric desymmetrization reaction of cyclopentenediones with enals has been successfully initiated, followed with tandem aldol annulation, aromatization, as well as sequential methylation. The reactions proceeded well under mild reaction conditions, with broad substrate scope and good functional group tolerance, providing a rapid access to highly functionalized chiral 2,2-disubstituted 1,3-indandione derivatives containing an all-carbon quaternary stereogenic center in moderate to good yields with high enantioselectivities.

10.
Sensors (Basel) ; 19(19)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547565

RESUMO

Real-time capturing of vehicle motion is the foundation of connected vehicles (CV) and safe driving. This study develops a novel vehicle motion detection system (VMDS) that detects lane-change, turning, acceleration, and deceleration using mobile sensors, that is, global positioning system (GPS) and inertial ones in real-time. To capture a large amount of real-time vehicle state data from multiple sensors, we develop a dynamic time warping based algorithm combined with principal component analysis (PCA). Further, the designed algorithm is trained and evaluated on both urban roads and highway using an Android platform. The aim of the algorithm is to alert adjacent drivers, especially distracted drivers, of potential crash risks. Our evaluation results based on driving traces, covering over 4000 miles, conclude that VMDS is able to detect lane-change and turning with an average precision over 76% and speed, acceleration, and brake with an average precision over 91% under the given testing data dataset 1 and 4. Finally, the alerting tests are conducted with a simulator vehicle, estimating the effect of alerting back or front vehicle the surrounding vehicles' motion. Nearly two seconds are gained for drivers to make a safe operation. As is expected, with the help of VMDS, distracted driving decreases and driving safety improves.

11.
Health Policy Plan ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31504504

RESUMO

Integrated nutrition and agricultural interventions have the potential to improve the efficiency and effectiveness of investments in food security and nutrition. This article aimed to estimate the costs of an integrated agriculture and health intervention (Mama SASHA) focused on the promotion of orange-fleshed sweet potato (OFSP) production and consumption in Western Kenya. Programme activities included nutrition education and distribution of vouchers for OFSP vines during antenatal care and postnatal care (PNC) visits. We used expenditures and activity-based costing to estimate the financial costs during programme implementation (2011-13). Cost data were collected from monthly expense reports and interviews with staff members from all implementing organizations. Financial costs totalled US$507 809 for the project period. Recruiting and retaining women over the duration of their pregnancy and postpartum period required significant resources. Mama SASHA reached 3281 pregnant women at a cost of US$155 per beneficiary. Including both pregnant women and infants who attended PNC services with their mothers, the cost was US$110 per beneficiary. Joint planning, co-ordination and training across sectors drove 27% of programme costs. This study found that the average cost per beneficiary to implement an integrated agriculture, health and nutrition programme was substantial. Planning and implementing less intensive integrated interventions may be possible, and economies of scale may reduce overall costs. Empirical estimates of costs by components are critical for future planning and scaling up of integrated programmes.

12.
Biomed Pharmacother ; 119: 109410, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518877

RESUMO

AIMS: The present study aimed to investigate the effect of metformin on diabetes-accelerated atherosclerosis and whether Nod-like receptor protein 3 (NLRP3) inflammasome is a target for metformin. MATERIALS AND METHODS: ApoE-/- male mice were divided randomly into control, streptozocin-induced diabetes mellitus and metformin groups. Metabolic parameters, atherosclerotic lesion, activation of NLRP3 inflammasomes and related signaling pathways were detected. THP-1-differentiated macrophages were used in in vitro experiments. RESULTS: Compared with control mice, increased plasma lipids and proinflammatory interleukin-1ß, aggravated macrophage infiltration into the atherosclerotic lesion, and accelerated development of atherosclerosis were observed in diabetic mice, which were associated with the activation of NLRP3 inflammasomes and dysregulation of thioredoxin-1 and thioredoxin-interacting protein. Treatment with metformin alleviated diabetes-induced metabolic disorders and atherosclerosis, as well as NLRP3 inflammasomes activation and dysregulation of thioredoxin-1/thioredoxin-interacting protein. In vitro experiments showed that high glucose induced the accumulation of reactive oxygen species and activated NLRP3 inflammasomes, which was significantly suppressed by treatment with metformin or antioxidant N-acetyl-L-cysteine. Moreover, Compound C, an inhibitor of adenosine 5'-monophosphate-activated protein kinase (AMPK), blocked the anti-inflammatory effect of metformin, indicating that metformin inhibited high glucose-induced NLRP3 inflammasomes activation through AMPK activation. Moreover, high glucose decreased thioredoxin-1 expression and increased thioredoxin-interacting protein expression, which was also reversed by metformin. CONCLUSIONS: Metformin inhibited NLRP3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice, which at least partially through activation of AMPK and regulation of thioredoxin-1/thioredoxin-interacting protein.

13.
Oncogene ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530934

RESUMO

Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction-oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31552514

RESUMO

Strain YIM PH21724T was isolated from the rhizosphere of Panax notoginseng. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strain exhibits close phylogenetic relatedness to Nocardia kroppenstedtii N1286T (97.70%), Nocardia farcinica NCTC 11134T (97.67%) and Nocardia puris DSM 44599T (97.40%). The menaquinones were identified as MK-9 (H4), MK-8 (H4, ω-cyclo) and MK-8 (H4), and the major fatty acids (> 10%) were identified as C16:0, C18:1 ω9c and C18:0 10-methyl. The polar lipids were found to be composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides and an unidentified lipid. The G + C content of the genomic DNA was determined to be 67.01 mol%. The phenotypic, chemotaxonomic, phylogenetic and genomic results clearly show strain YIM PH21724T should be classified in the genus Nocardia and represents a novel species, for which the name Nocardia panacis sp. nov. is proposed. The type strain is YIM PH21724T (= DSM 105904T = KCTC 49030T = CCTCC AA 2017043T).

15.
Zhongguo Gu Shang ; 32(8): 750-755, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31533389

RESUMO

OBJECTIVE: To explore infection rate of different adeno-associated virus (AAV) on knee joint cartilage in mice and to find a good gene editing tool for mice chondrocytes of knee joint. METHODS: Forty-five 4-week-old SPF C57BL/6 weighed(14.3±0.2) g were selected. According to different injections(6 µl) for right knee joint, mice were divided into 9 different groups, 5 mice in each group. The groups were such as following:control group (normal saline), Vigene 2 group (AAV2 from vigene biosciences, titer for 1×10¹³ vg/ml), Vigene 5 group (AAV5 from vigene biosciences, titer for 1×10¹³ vg/ml), Vigene 6 group (AAV6 from vigene biosciences, titer for 1×10¹³ vg/ml), Vigene 7 group (AAV7 from vigene biosciences, titer for 1×10¹³ vg/ml), Vigene 8 group (AAV8 from vigene biosciences, titer for 1×10¹³ vg/ml), Vigene 9 group (AAV9 from vigene biosciences, titer for 1×10¹³ vg/ml), Hanbio DJ group(AAV2-DJ from Hanbio, titer for 1×10¹² vg/ml), Hanbio 5 group (AAV5 from Hanbio, titer for 1×10¹² vg/ml). All AAVs were over-expressed green fluorescent protein(GFP). Knee joint specimens were taken and observed injury of cartilage under stereomicroscope at 30 days after injection, then 10 µm thick frozen sections were prepared. Distribution of green fluorescent protein of meniscus and cartilage of knee joint was observed under fluorescence microscope. RESULTS: Stereomicroscope observation indicated that no obvious lesion was observed in knee joint cartilage of mice after intra-articular injection of AAV. According to frozen sections of knee joints, strong green fluorescence was observed in knee joint cartilage in all AAV experimental groups. Compared with other groups, significantly stronger green fluorescence were observed both in AAV2 and AAV7 groups, whose average fluorescence density was 0.077±0.020 and 0.061±0.022. There were significant differences between two groups and other groups. CONCLUSIONS: AAV could infect chondrocyte of knee joint in vivo by injecting into knee joint cavity. Higher infection efficiency of AAV2 and AAV7 on knee joint cartilage were observed. Local injection of AAV into knee joint cavity could be used as an effective tool for gene editing of knee joint chondrocyte.


Assuntos
Dependovirus , Articulação do Joelho , Animais , Cartilagem , Proteínas de Fluorescência Verde , Camundongos , Camundongos Endogâmicos C57BL
16.
Mitochondrial DNA A DNA Mapp Seq Anal ; 30(7): 786-793, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31542986

RESUMO

Domestic Bactrian camel (Camelus bactrianus) used to be one of the most important livestock species in Chinese history, as well as the major transport carrier on the ancient Silk Road. However, archeological studies on Chinese C. bactrianus are still limited, and molecular biology research on this species is mainly focused on modern specimens. In this study, we retrieved the complete mitochondrial genome from a C. bactrianus specimen, which was excavated from northwestern China and dated at 1290-1180 cal. years before present (yBP). Phylogenetic analyses using 18 mitochondrial genomes indicated that the C. bactrianus clade was divided into two maternal lineages. The majority of samples originating from Iran to Japan and Mongolia belong to subclade A1, while our sample together with two Mongolian individuals formed the much smaller subclade A2. Furthermore, the divergence time of these two maternal lineages was estimated as 165 Kya (95% credibility interval 117-222 Kya), this might indicate that several different evolutionary lineages were incorporated into the domestic gene pool during the initial domestication process. Bayesian skyline plot (BSP) analysis suggest a slow increase in female effective population size of C. bactrianus from 5000 years ago, which corresponds to the beginning of domestication of C. bactrianus. The present study also revealed that there were extensive exchanges of genetic information among C. bactrianus populations in regions along the Silk Road.

17.
Complement Ther Med ; 46: 180-188, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31519276

RESUMO

BACKGROUND: N-of-1 trial is a desired and appropriate approach to assessing the efficacy and safety of traditional Chinese medicine (TCM) interventions. There have been an increasing number of N-of-1 trials for TCM published. However, a lack of preferred reporting guidance led in the general poor reporting quality of these trials. Due to the unique characteristics of TCM, the working group developed this CONSORT Extension for reporting N-of-1 Trials for Traditional Chinese Medicine (CENT for TCM) to assist TCM researchers in reporting N-of-1 trials for TCM. METHODS: We registered CENT for TCM at the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network (available at equator-network.org). The development was a comprehensive process through collection of the initial reporting items, two-round scientific Delphi consensus survey with 17 panelists, revision and formation of the final reporting checklist. RESULTS: The checklist includes 25 items within six domains, eight items in which were extended and elaborated on the items of the CENT 2015 checklist. Explanation of the items were listed adequately considering the nature of TCM, introducing the concept of TCM syndrome differentiation and TCM interventions. CONCLUSIONS: CENT for TCM can be used to assess the completeness of the reporting of N-of-1 trials for TCM. The working group expect that CENT for TCM could be a practical tool to enhance the comprehensiveness and transparency of the design, implementation and reporting of N-of-1 trials for TCM.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31511971

RESUMO

PURPOSE: The role of lymph node ratio (LNR, ratio of metastatic to examined nodes) in the staging of multiple human malignancies has been reported. We aim to evaluate its value in salivary gland cancer (SGC). METHODS: Records of SGC patients from Surveillance, Epidemiology, and End Results database (SEER, training set, N = 4262) and Fudan University Shanghai Cancer Center (FUSCC, validating set, N = 154) were analyzed for the prognostic value of LNR. Kaplan-Meier survival estimates, the Log-rank χ2 test and Cox proportional hazards model were used for univariate and multivariate analysis. Optimal LNR cutoff points were identified by X-tile. RESULTS: Optimal LNR cutoff points classified patients into four risk groups, R0, R1 (≤ 0.17), R2 (0.17-0.56) and R3 (> 0.56), corresponding to 5-year cause-specific survival in SEER patients of 88.6%, 57.2%, 53.1% and 39.7%, disease-free survival in FUSCC patients of 69.2%, 63.3%, 34.6% and 0%, and disease-specific survival in FUSCC patients of 92.3%, 90.0%, 71.4% and 0%, respectively. Compared with TNM staging, TNM + R staging showed smaller AIC values and higher C-index values in the Cox regression model in both patient sets. CONCLUSIONS: LNR classification should be considered as a complementary system to TNM staging and LNR classification based clinical trials deserve further research.

19.
Neurosurgery ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501892

RESUMO

BACKGROUND: Currently, little is known about the clinical relevance of tumor-stroma ratio (TSR) in chordoma and data discussing the relationship between TSR and immune status of chordoma are lacking. OBJECTIVE: To characterize TSR distribution in spinal chordoma, and investigated its correlation with clinicopathologic or immunological features of patients and outcome. METHODS: TSR was assessed visually on hematoxylin and eosin-stained sections from 54 tumor specimens by 2 independent pathologists. Multiplex immunofluorescence was used to quantify the expression levels of microvessel density, Ki-67, Brachyury, and tumor as well as stromal PD-L1. Tumor immunity status including the Immunoscore and densities of tumor-infiltrating lymphocytes (TILs) subtypes were obtained from our published data and reanalyzed. RESULTS: Bland-Altman plot showed no difference between mean TSR derived from the two observers. TSR was positively associated with stromal PD-L1 expression, the Immunoscore and CD3+ as well as CD4+ TILs density, but negatively correlated with tumor microvessel density, Ki-67 index, surrounding muscle invasion by tumor and number of Foxp3+ and PD-1+ TILs. Low TSR independently predicted poor local recurrence-free survival and overall survival. Moreover, patients with low TSR and low Immunoscore chordoma phenotype were associated with the worst survival. More importantly, combined TSR and Immunoscore accurately reflected prognosis and enhanced the ability of TSR or Immunoscore alone for outcome prediction. CONCLUSION: These data reveal the significant impact of TSR on tumor progression and immunological response of patients. Subsequent use of agents targeting the stroma compartment may be an effective strategy to treat chordoma especially in combination with immune-based drugs.

20.
Cell Signal ; 65: 109419, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31526829

RESUMO

Cancer cells with stem cell properties have been acknowledged to be responsible for cancer initiation and progression. Wnt/ß-catenin signalling is a major signal pathway promoting the stemness of cancer cells. Anterior gradient 3 (AGR3), a member of the protein disulfide isomerase (PDI) family, was found to be overexpressed in several cancers. However, the roles and mechanisms of AGR3 in colorectal cancer (CRC) have not been previously described. In our study, we find that AGR3 is highly expressed in CRC and associated with poor prognosis. Functional studies show that AGR3 promotes the stemness of CRC cells. Mechanically, AGR3 activates Wnt/ß-catenin signalling and promotes the nuclear translocation of ß-catenin to upregulate stemness related genes. Wnt/ß-catenin signalling inhibition counteracts the promoting effect of AGR3 on cancer stemness. Moreover, the effect of AGR3 on Wnt/ß-catenin signalling and cancer stemness depends on the presence of frizzled 4 (FZD4). Thus, our study first uncovers the stemness-promoting role and the oncogenic mechanism of AGR3 in CRC, which might provide a novel target for designing anti-CRC strategies.

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