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1.
Artigo em Inglês | MEDLINE | ID: mdl-31425724

RESUMO

BACKGROUND: Schizophrenia (SCZ) is a severe mental disorder. Both environmental and genetic factors contribute to the development of SCZ. The estimated heritability of SCZ is about 80%. Previous genetic studies of SCZ mainly focused on the genetic variations associated the risk of SCZ. Limited efforts are paid to explore the roles and biological mechanism of nuclear acid methylation implicated in the pathogenesis of SCZ. METHODS: A two-stage integrative analysis of SCZ GWAS and nuclear acid methylation functional annotation data (including meQTLs and m6A) was performed in this study. First, the discovery GWAS of SCZ was aligned with genomic meQTLs and m6A annotation data to identify the candidate genes associated with SCZ. Second, another independent replication GWAS dataset of SCZ was applied to validate the discovery results. Furthermore, the functional relevance of identified candidate genes with SCZ were validated by the mRNA expression profiling of SCZ brain tissues. Gene ontology (GO) and pathway enrichment analysis of identified candidate genes was performed by the DAVID tool. RESULTS: The two-stage integrative analysis detected 106 meQTLs related candidate genes for SCZ. After comparing with the differentially expressed genes in SCZ brain tissues, 49 overlapped genes were identified for meQTLs, such as ZSCAN12, BTN3A2 and HLA-DQA1. Besides, for meQTLs, 29 SCZ associated pathways and 56 SCZ associated GO terms were detected, such as cell adhesion molecules and asthma. For m6A, 25 candidate genes were detected by the two-stage integrative analysis for SCZ, such as ZSCAN12, HLA-DQA1 and SNX19. Furthermore, 17 of the 25 genes were detected in the mRNA expression profiling of SCZ brain tissues. CONCLUSION: This study identified multiple SCZ associated genes and pathways, supporting the implication of nuclear acid methylation in the pathogenesis of SCZ.

2.
Biomed Pharmacother ; 121: 109615, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707343

RESUMO

Psoriasis is considered an immune-mediated inflammatory skin disorder that affects the quality of life of nearly four percent of the world population. Considering the side effects of existing therapeutic drugs and the urgent need for new drug development, we screened more than 250 traditional Chinese medicine compounds to identify drugs that significantly reduced the viability of human HaCaT keratinocytes, a psoriasis-related model cell line. Convallatoxin (CNT) was found to be a highly effective inhibitor of HaCaT cell viability. Subsequent mechanistic studies revealed that CNT induced HaCaT cell death by necroptosis rather than by apoptosis. CNT destroyed the membrane integrity of HaCaT cells, as detected by nuclear propidium iodide (PI) staining and lactate dehydrogenase (LDH) release. Additionally, the intercellular levels of adenosine triphosphate (ATP) were lower in HaCaT cells treated with CNT than in control HaCaT cells, and typical necroptosis-associated characteristics were observed by electron microscopy in cells treated with CNT. Furthermore, compared with control HaCaT cells, CNT-treated HaCaT cells produced more reactive oxygen species (ROS), but this effect was inhibited by the antioxidants N-acetyl-cysteine (NAC), diphenyleneiodonium chloride (DPI), and apocynin and the necroptosis inhibitor Nec-1. In addition, antioxidant treatment attenuated necroptotic cell death, suggesting that CNT-induced HaCaT necroptosis is mediated by oxidative stress. More importantly, CNT ameliorated skin lesions and inflammation in imiquimod (IMQ)- and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced psoriasis-like mouse models. In conclusion, our results demonstrate that CNT is cytotoxic against HaCaT cells in vitro and exerts antipsoriatic activities in two mouse models of psoriasis in vivo, making CNT a potential promising candidate drug for future research.

3.
Chemosphere ; 240: 124936, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31568941

RESUMO

Triphenyltin (TPT) is widely used and commonly found in a water environment, so its effects on aquatic systems are of great concern. This study aimed to reveal the effects of chronic parental exposure of TPT on thyroid disruption and growth inhibition in zebrafish. Adult zebrafish (F0 generation) were exposed to environmentally relevant concentrations (1, 10, and 100 ng/L) of TPT for 60 days, and the larvae (F1 generation) were tested without TPT treatment. Results demonstrated that parental exposure to TPT disrupts thyroid function in zebrafish offspring: serum thyroxine (T4) significantly decreased, while serum 3,5,3'-triiodothyronine (T3) increased, and several genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were down-regulated. In addition, we observed developmental abnormalities in the larvae, demonstrated by a significantly altered hatching rate, malformation rate, body length, heart rate, and survival rate, as well as down-regulation of genes involved in the growth hormone/insulin-like growth factor (GH/IGF) axis. Therefore, parental exposure to TPT induces toxicity in fish offspring through perturbation of the HPT and GH/IGF axes.

4.
Talanta ; 207: 120285, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594625

RESUMO

Detection of microRNAs (miRNAs) in cells improves our understanding of their physiological functions and facilitates exploration of their roles diseases. The toehold-mediated strand displacement reaction initiates rolling circle amplification (RCA) to achieve signal amplification of the specific miRNA; This process is named as toehold-initiated RCA (TIRCA). The product of TIRCA was ligated to two DNA probes, which were modified with 6-carboxyfluorescein and carboxytetramethylrhodamine, respectively. Qualitative detection of miRNAs was successfully achieved by combining the fluorescence aggregation enhancement effect with fluorescence resonance energy transfer generated by the proximity of the two fluorescent dyes. Thus, this approach helps us analyze the roles of miRNAs in human disease more accurately.

5.
Biochim Biophys Acta Gen Subj ; 1864(1): 129422, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31491457

RESUMO

BACKGROUND: Previous studies suggested that fibrillar human IAPP (hIAPP) is more likely to deposit in ß-cells, resulting in ß-cell injury. However, the changes in the conformation of hIAPP in lipid environment and the mechanism involved in ß-cell damage are unclear. METHODS: Synthetic hIAPP was incubated with five types of free fatty acids and phospholipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS), which constitute the cell membrane. Thioflavin-T fluorescence assay was conducted to analyze the degree of hIAPP fibrosis, and circular dichroism spectroscopy was performed to detect the ß-fold formation of hIAPP. Furthermore, INS-1 cells were infected with human IAPP delivered by a GV230-EGFP plasmid. The effects of endogenous hIAPP overexpression induced by sodium palmitate on the survival, endoplasmic reticulum (ER) stress, and apoptosis of INS-1 cells were evaluated. RESULTS: The five types of free fatty acids can accelerate the fibrosis of hIAPP. Sodium palmitate also maintained the stability of fibrillar hIAPP. POPS, not POPC, accelerated hIAPP fibrosis. Treatment of INS-1 cells with sodium palmitate increased the expression of hIAPP, activated ER stress and ER stress-dependent apoptosis signaling pathways, and increased the apoptotic rate. CONCLUSION: Free fatty acids and anionic phospholipid can promote ß-fold formation and fibrosis in hIAPP. High lipid induced the overexpression of hIAPP and aggravated ER stress and apoptosis in INS-1 cells, which caused ß-cell death in high lipid environment. GENERAL SIGNIFICANCE: Our study reveals free fatty acids and hIAPP synergistically implicated in endoplasmic reticulum stress and apoptosis of islet ß-cells.

6.
IEEE Trans Cybern ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31794419

RESUMO

Symmetry detection is a method to extract the ideal mid-sagittal plane (MSP) from brain magnetic resonance (MR) images, which can significantly improve the diagnostic accuracy of brain diseases. In this article, we propose an automatic symmetry detection method for brain MR images in 2-D slices based on a 2-channel convolutional neural network (CNN). Different from the existing detection methods that mainly rely on the local image features (gradient, edge, etc.) to determine the MSP, we use a CNN-based model to implement the brain symmetry detection, which does not require any local feature detections and feature matchings. By training to learn a wide variety of benchmarks in the brain images, we can further use a 2-channel CNN to evaluate the similarity between the pairs of brain patches, which are randomly extracted from the whole brain slice based on a Poisson sampling. Finally, a scoring and ranking scheme is used to identify the optimal symmetry axis for each input brain MR slice. Our method was evaluated in 2166 artificial synthesized brain images and 3064 collected in vivo MR images, which included both healthy and pathological cases. The experimental results display that our method achieves excellent performance for symmetry detection. Comparisons with the state-of-the-art methods also demonstrate the effectiveness and advantages for our approach in achieving higher accuracy than the previous competitors.

7.
Aging (Albany NY) ; 112019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31794427

RESUMO

Ninjurin2 (Ninj2) is an adhesion protein expressed in neurons and glial cells. The current study tested its expression and potential functions in human glioma. We show that Ninj2 mRNA and protein levels are significantly upregulated in human glioma cells and tissues. In established and primary human glioma cells, Ninj2 shRNA or knockout (by CRISPR/Cas9 gene editing) potently inhibited cell survival, growth, proliferation, cell migration and invasion, while inducing apoptosis activation. Contrarily, ectopic overexpression of Ninj2 promoted glioma cell progression in vitro. In human glioma tissues and cells, Ninj2 co-immunoprecipitated with multiple receptor tyrosine kinases (EGFR, PDGFRß and FGFR), required for downstream Akt and Erk activation. Akt and Erk activation was potently inhibited by Ninj2 shRNA or knockout, but enhanced with ectopic Ninj2 overexpression in glioma cells. In summary, we show that Ninj2 overexpression promotes glioma cell growth.

8.
Reproduction ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786538

RESUMO

Small extracellular vesicles (sEVs) are important mediators of cell-to-cell communication involved in successful establishment of a pregnancy. Human decidual stromal cells play a key role in regulating trophoblast invasion. Nevertheless, the regulatory functions of decidual stromal cells-derived sEVs in human trophoblast cells are still unclear. In this study, primary human decidual stromal cells were isolated and immortalized human endometrial stromal cell line (HESCs) were decidualised into human decidual stromal cells (HDSC) using hormonal cocktail containing Medroxy progesterone 17-acetate (MPA), estrogen and cAMP analog. HDSC-sEVs were isolated from both primary human decidual stromal cells and immortal HDSCs respectively, and identified by transmission electron microscopy and western blotting. EVs up-taken assay indicated that HDSC-sEVs could be up-taken by trophoblast cells. HDSC-sEVs could increase the invasiveness and the expression level of N-cadherin of trophoblast cells with elevated phosphorylation of SMAD2 and SMAD3 in the cells. Silencing of N-cadherin could block cell invasion induced by HDSC-sEVs, while knockdown of SMAD2 and SMAD3 could inhibit the up-regulation of N-cadherin in trophoblast cells. Taken together, our results suggested a regulatory effect of HDSC-sEVs in the invasion of trophoblast cells, and HDSC-sEVs may be important mediators of trophoblasts during embryo implantation and placentation.

9.
ACS Nano ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31800218

RESUMO

The continuing increase of the efficiency of perovskite solar cells has pushed the internal quantum efficiency approaching 100%, which means the light-to-carrier and then the following carrier transportation and extraction are no longer limiting factors in photoelectric conversion efficiency of perovskite solar cells. However, the optimal efficiency is still far lower than the Shockley-Queisser efficiency limit, especially for those inverted perovskite solar cells, indicating significant fraction of light do not transmit into the active perovskite layer to be absorbed there. Here a planar inverted perovskite solar cell (ITO/PTAA/perovskite/PC61BM/bathocuproine (BCP)/Ag) is chosen as an example and we show that the external quantum efficiency (EQE) of it can be significantly improved by simply texturing the Poly [bis (4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA) layer. By washing the film prepared from mixed polymer solution of PTAA and Polystyrene (PS), a textured PTAA/perovskite interface is introduced on the light-input side of perovskite to inhibit internal optical reflection. The reduction of optical loss by this simple texture method increases the EQE and then the photocurrent of ITO/PTAA/perovskite/PC61BM/BCP/Ag device with the magnitude about 10%. At the same time, this textured PTAA benefits the band edge absorption in this planar solar cell. The large increase of the short-circuit current together with the increase of fill factor pushes the efficiency of this inverted perovskite solar cell from 18.3% up to an efficiency over 20.8%. By using anti-reflection coating on glass to let more light into the device, the efficiency is further improved to 21.6%, further demonstrating the importance of light management in perovskite solar cells.

10.
Anal Chem ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31800227

RESUMO

The development of on-tissue chemical derivatization methods for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) of small endogenous metabolites in tissues has attracted great attention for their advantages in improving detection sensitivity and ionization efficiency of poorly ionized and low abundant metabolites. Herein, a laser-assisted tissue transfer (LATT) technique was developed to enhance on-tissue derivatization of small molecules. Using a focused blue laser, a thin-layer tissue film (~ 1 µm) was transferred to an acceptor slide from a 6 µm dry tissue section preliminarily coated with derivatization and matrix reagents. The acceptor slide with its ablated constituents was then imaged by MALDI MS. On-tissue chemical derivatization with amino-specific derivatization reagent 4-hydroxy-3-methoxycinnamaldehyde (CA) was carried out on LATT system. 20-235 folds increase in signal intensity for CA derivatized metabolites such as amino acids, neurotransmitters and dipeptides were observed from rat brain tissues in comparison with conventional incubation-based derivatization. This technique was further extended to derivatize steroids with Girard reagent T (GirT). The remarkable derivatization efficiency can mainly be attributed to the minimization of ion suppression effects due to the reduced thickness of tissue section and endogenous components. Additionally, shorter derivatization time with no obvious metabolite delocalization was achieved using LATT method. These results demonstrate the advantages of LATT in the enhancement of on-tissue derivatization for the more specific and sensitive imaging of small metabolites in tissues with MALDI MS.

11.
Environ Microbiol ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31797523

RESUMO

Rice false smut has emerged as a serious grain disease in rice production worldwide. The disease is characterized by the transformation of individual rice florets into false smut balls, which is caused by the fungal pathogen Ustilaginoidea virens. To date, little is known about the host factors required for false smut ball formation by U. virens. In this study, we identified histological determinants for the formation of false smut balls by inoculating U. virens into rice floral mutants defective with respect to individual floral parts. The results showed that U. virens could form mature false smut balls in rice floral mutants with defective pistils, but failed to develop false smut balls in the superwoman mutant lacking stamens, identifying that U. virens requires rice stamens to complete its infection cycle. Comparative transcriptome analysis indicated a list of candidate host genes that may facilitate nutrient acquisition by U. virens from the rice stamens, such as SWEET11, SWEET14 and SUT5, and genes involved in the biosynthesis of trehalose and raffinose family sugars. These data pinpoint rice stamens as the key target organ of U. virens infection, and provide a valuable starting point for dissecting the molecular mechanism of false smut ball formation. This article is protected by copyright. All rights reserved.

12.
World J Gastroenterol ; 25(43): 6451-6464, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31798281

RESUMO

BACKGROUND: Because of the powerful abilities of self-learning and handling complex biological information, artificial neural network (ANN) models have been widely applied to disease diagnosis, imaging analysis, and prognosis prediction. However, there has been no trained preoperative ANN (preope-ANN) model to preoperatively predict the prognosis of patients with gastric cancer (GC). AIM: To establish a neural network model that can predict long-term survival of GC patients before surgery to evaluate the tumor condition before the operation. METHODS: The clinicopathological data of 1608 GC patients treated from January 2011 to April 2015 at the Department of Gastric Surgery, Fujian Medical University Union Hospital were analyzed retrospectively. The patients were randomly divided into a training set (70%) for establishing a preope-ANN model and a testing set (30%). The prognostic evaluation ability of the preope-ANN model was compared with that of the American Joint Commission on Cancer (8th edition) clinical TNM (cTNM) and pathological TNM (pTNM) staging through the receiver operating characteristic curve, Akaike information criterion index, Harrell's C index, and likelihood ratio chi-square. RESULTS: We used the variables that were statistically significant factors for the 3-year overall survival as input-layer variables to develop a preope-ANN in the training set. The survival curves within each score of the preope-ANN had good discrimination (P < 0.05). Comparing the preope-ANN model, cTNM, and pTNM in both the training and testing sets, the preope-ANN model was superior to cTNM in predictive discrimination (C index), predictive homogeneity (likelihood ratio chi-square), and prediction accuracy (area under the curve). The prediction efficiency of the preope-ANN model is similar to that of pTNM. CONCLUSION: The preope-ANN model can accurately predict the long-term survival of GC patients, and its predictive efficiency is not inferior to that of pTNM stage.

13.
Biochim Biophys Acta Mol Basis Dis ; : 165625, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31785406

RESUMO

One of the hallmarks of cancer progression is strong drug resistance during clinical treatments. The tumor microenvironment is closely associated with multidrug resistance, the optimization of tumor microenvironments may have a strong therapeutic effect. In this study, we configured polyacrylamide hydrogels of varying stiffness [low (10 kPa), intermediate (38 kPa) and high (57 kPa)] to simulate tissue physical matrix stiffness across different stages of breast cancer. After treatment with doxorubicin, cell survival rates on intermediate stiffness substrate are significantly higher. We find that high expression of ILK and YAP reduces the survival rates of breast cancer patients. Drug resistance is closely associated with the inactivation of the hippo pathway protein Merlin/MST/LATS and the activation of YAP. These results not only highlight the understanding of drug resistance mechanisms but also serve as a new basis for developing breast cancer treatment delivery systems.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31785812

RESUMO

Endoplasmic reticulum (ER) stress is a conserved cellular process for cells to clear unfolded or misfolded proteins and maintain cell homeostasis under stress conditions. Autophagy may act as a pro-survival strategy to cope with multiple stress conditions in tumor progression and distant metastasis. Although many studies have demonstrated that there is a close correlation between radiation-induced ER stress and autophagy, the molecular mechanisms currently remain unclear. In the present study, we performed an in vivo study concerning the effect of autophagy induced by ER stress on the radiosensitivity of mouse sarcoma using X-rays. Our results documented that X-rays could induce ER stress in sarcoma and then autophagy was activated by unfolded protein response (UPR) through the IRE1-JNK-pBcl2-Beclin1 signaling axis. The induction of autophagy caused a decline in cell apoptosis while inhibiting the autophagy resulted in increased apoptosis and inhibition of tumor progression. Combined treatment of X-ray exposure and chloroquine increased ER stress-related apoptosis and enhanced the radiosensitivity of mouse sarcoma that was not sensitive to X-ray irradiation alone. Thus, our study indicates that inhibition of ER stress-induced autophagy might be a novel strategy to improve the efficacy of radiotherapy against radioresistant sarcoma.

15.
J BUON ; 24(5): 2161-2167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31786890

RESUMO

PURPOSE: Although clinical indicators provide effective prognostic information, the prognosis of melanoma is difficult due to its genomic and biological complexity. Our goal was to elucidate the impact of genes on survival. METHODS: Public cohorts of melanoma gene expression and machine learning were used to develop a model for prognosis. A four-gene model was developed to predict the clinical outcome of melanoma in TCGA datasets. The performance was further validated in four independent cohorts. The relationship between clinical indicators and melanoma score was assayed and the correlated pathways were identified. RESULTS: The samples with high melanoma scores had a significantly better survival rate than those with low melanoma scores in the training cohort. This observation was confirmed in four independent cohorts, GSE22138, GSE54467, GSE65904 and E-MTAB-4725. In addition, the melanoma score was independent of most clinically used indicators. Cox univariate regression showed that the melanoma score was significantly associated with survival. Multiple significantly enriched pathways were identified between the high-score and low-score groups.

16.
Biotechnol Bioeng ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31788785

RESUMO

Natural tissues are incorporated with vasculature which is further integrated with a cardiovascular system responsible for driving perfusion of nutrient-rich oxygenated blood through the vasculature in order to support cells metabolism within most cell-dense tissues. Since scaffold-free biofabricated tissues being developed into clinical implants, research models, and pharmaceutical testing platforms should similarly exhibit perfused tissue-like structures, we generated a generalizable biofabrication method resulting in Self-Supporting Perfused (SSuPer) tissue constructs incorporated with perfusible microchannels and integrated with the modular FABRICA perfusion bioreactor. As proof of concept, we perfused an MLO-A5 osteoblast-based SSuPer tissue in the FABRICA. Although our resulting SSuPer tissue replicated vascularization and perfusion observed in situ, supported its own weight, and stained positively for mineral using Von Kossa staining, our in vitro results indicated that computational fluid dynamics (CFD) should be used to drive future construct design and flow application prior to further tissue biofabrication and perfusion. We built a CFD model of the SSuPer tissue integrated in the FABRICA and analyzed flow characteristics (net force, pressure distribution, shear stress, and oxygen distribution) through five SSuPer tissue microchannel patterns in two flow directions and at increasing flow rates. Important flow parameters include flow direction, fully-developed flow, and tissue microchannel diameters matched and aligned with bioreactor flow channels. We observed that the SSuPer tissue platform is capable of providing direct perfusion to tissue constructs and proper culture conditions (oxygenation, with controllable shear and flow rates), indicating that our approach can be used to biofabricate tissue representing primary tissues and that we can model the system in silico. This article is protected by copyright. All rights reserved.

17.
Ecotoxicol Environ Saf ; : 109987, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31784104

RESUMO

This study evaluated the relationship between urine mercury (UHg) concentrations and renal function (serum creatinine (SCr) and blood urea nitrogen (BUN)) in delivery women in the Wanshan mercury (Hg) mining area. Leishan County was selected as the control area. 165 and 65 maternal samples were collected from the Wanshan and Leishan area, respectively. The geometric means of UHg concentrations were 1.09 and 0.29 µg/L in Wanshan and Leishan subjects, respectively. Significant differences (p < 0.01) of UHg were observed between the two populations, indicating the potential risks of inorganic Hg exposure in the Wanshan population. The median (interquartile range) values of SCr were 69.1 (12.5) µmol/L and 46.0 (11.0) µmol/L for the Wanshan and Leishan populations, respectively, indicating significant differences (p < 0.01) between the two groups. However, no significant differences among BUN values for the two groups were observed. A significant positive correlation (r = 0.385, p < 0.001) was observed between UHg concentration and SCr in the study population. The odds ratio (OR) value of UHg in Wanshan area was 9.29 times higher than that in Leishan area (95% confidence interval (CI): 3.58-24.1). The OR value of SCr decrease in patients with low UHg was 0.32 times higher than that in patients with high UHg (95% CI: 0.19-0.55). The OR value of SCr decrease in the population with fish consumption was 0.71 times higher than that of the population without fish consumption (95% CI: 0.58-0.88). In conclusion, maternal IHg exposure caused impaired renal function and fish consumption may play a role in preventing Hg-induced nephrotoxicity.

18.
BMC Gastroenterol ; 19(1): 205, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791240

RESUMO

PURPOSE: To determine the indications for adjuvant chemotherapy (AC) in patients with stage IIa gastric cancer (T3N0M0 and T1N2M0) according to the 7th American Joint Committee on Cancer (AJCC). METHODS: A total of 1593 patients with T3N0M0 or T1N2M0 stage gastric cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database for the period 1988.1-2012.12. Cox multiple regression, nomogram and decision curve analyses were performed. External validation was performed using databases of the Fujian Medical University Union Hospital (FJUUH) (n = 241) and Italy IMIGASTRIC center (n = 45). RESULTS: Cox multiple regression analysis showed that the risk factors that affected OS in patients receiving AC were age > 65 years old, T1N2M0, LN dissection number ≤ 15, tumor size > 20 mm, and nonadenocarcinoma. A nomogram was constructed to predict 5-year OS, and the patients were divided into those predicted to receive a high benefit (points ≤ 188) or a low benefit from AC (points > 188) according to a recursive partitioning analysis. OS was significantly higher for the high-benefit patients in the SEER database and the FJUUH dataset than in the non-AC patients (Log-rank < 0.05), and there was no significant difference in OS between the low-benefit patients and non-AC patients in any of the three centers (Log-rank = 0.154, 0.470, and 0.434, respectively). The decision curve indicated that the best clinical effect can be obtained when the threshold probability is 0-92%. CONCLUSION: Regarding the controversy over whether T3N0M0 and T1N2M0 gastric cancer patients should be treated with AC, this study presents a predictive model that provides concise and accurate indications. These data show that high-benefit patients should receive AC.

19.
Diagn Microbiol Infect Dis ; : 114953, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31791809

RESUMO

Stenotrophomonas maltophilia is a pathogen with unique resistance patterns. We assessed 70 combat casualties with S. maltophilia clinical isolates to examine its role as a nosocomial pathogen in critically-ill trauma patients. Incidence density was 0.36 S. maltophilia infections per 100 patient-days (95% CI: 0.29-0.44). Patients predominantly had blast trauma (97%) and were critically injured (injury severity score [ISS] >25; 80%). Restricting to patients with ISS >15, 50 patients with S. maltophilia infections were compared to 441 patients with infections attributed to other gram-negative bacilli. Patients with S. maltophilia infections had significantly more operating room visits prior to isolation, traumatic or early surgical amputations, longer hospitalization (median 71 vs 47 days), and higher overall mortality (10% vs 2%; P = 0.01). Initial and serial (≥7 days between initial and subsequent isolation) S. maltophilia isolates had high susceptibility to trimethoprim-sulfamethoxazole and minocycline. Evaluation of newer agents awaiting CLSI breakpoints, including moxifloxacin, showed promising results.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31791946

RESUMO

In the past decades, the incidence of cryptococcosis has increased dramatically, which poses a new threat to human health. However, only a few drugs are available for the treatment of cryptococcosis. Here, we described the leading compound NT-a9, an analogue of isavuconazole, that showed strong antifungal activities in vitro and in vivo NT-a9 showed wide range activities against several pathogenic fungi in vitro, including Cryptococcus neoformans, Cryptococcus gattii, Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata and Candida parapsilosis, with MIC values ranging from 0.002 to 1 µg/ml. Particularly, NT-a9 exhibited excellent efficacy against C. neoformans with MIC value as low as 0.002 µg/ml. NT-a9 treatment resulted in changes in sterols content in C. neoformans, similar to fluconazole. In addition, NT-a9 possessed a relatively low cytotoxicity and high selectivity index. The in vivo efficacy of NT-a9 was assessed using a murine disseminated cryptococcosis model. Mice were infected intravenously with 1.8 ¡Á 106 CFU C. neoformans H99. In the survival study, NT-a9 significantly prolonged mice survival time compared with the control group, the isavuconazole, fluconazole or amphotericin B treated groups. Especially, 4 and 8 mg/kg of NT-a9 rescued all the mice with a survival of 100%. In the fungal burden study, NT-a9 also significantly reduced fungal burden in brains and lungs, while fluconazole and amphotericin B only reduced fungal burden in lungs. Taken together, these data suggested that NT-a9 is a promising antifungal candidate for the treatment of cryptococcosis infection.

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