Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.890
Filtrar
1.
J Neurochem ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31758799

RESUMO

Local anesthetics can cause severe toxicity when absorbed systemically. Rapid intravenous administration of lipid emulsion (LE) is the standard of care for severe local anesthetic systemic toxicity which can cause cardiovascular and central nervous system (CNS) injury. The biological mechanism by which LE alleviates CNS toxicity is unknown and understudied. Previous research has suggested that local anesthetics cause an imbalance of excitatory and inhibitory transmission in the brain. Therefore, this study aimed to observe the effect of LE on glutamate- and GABA-induced currents in CA1 pyramidal neurons after bupivacaine-induced CNS toxicity. We further characterized postsynaptic modifications in these cells to try to elucidate the mechanism by which LE mediates bupivacaine-induced CNS toxicity. Sprague Dawley rats received intravenous bupivacaine (1 mg kg-1  min-1 ) in either normal saline or LE (or LE without bupivacaine) for 5 min. An acute brain slice preparation and a combination of whole cell patch clamp techniques and whole cell recordings were used to characterize action potential properties, miniature excitatory and inhibitory post-synaptic currents, and postsynaptic modifications of excitatory and inhibitory transmission in CA1 hippocampal pyramidal neurons. The expression level of GABAA receptors were assessed with Western blotting, while H&E and TUNEL staining were used to assess cytoarchitecture and apoptosis levels, respectively. Bupivacaine treatment significantly increased the number of observed action potentials, while significantly decreasing rheobase, the first interspike interval(ISI), and hyperpolarization-activated cation currents (Ih) in CA1 pyramidal neurons. LE treatment significantly reduced the frequency of mIPSCs and enhanced GABA-induced paired pulse ratio with 50ms interval stimulation in bupivacaine-treated rats. Regulation of GABAA levels is a promising mechanism by which LE may ameliorate CNS toxicity after systemic absorption of bupivacaine.

2.
Chin Med J (Engl) ; 132(22): 2705-2715, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31725455

RESUMO

BACKGROUND: Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. METHODS: The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. RESULTS: Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. CONCLUSION: Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.

3.
BMC Cancer ; 19(1): 1049, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694577

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is characterized by its clinical and biological heterogeneity. The clinical prognostic implications of tumor-associated macrophages (TAMs) in DLBCL remain controversial and the correlation between TAMs and peripheral absolute monocyte count (AMC) has not yet been elucidated. METHODS: In 221 untreated, newly diagnosed patients with DLBCL, we evaluated the prognostic value of TAMs using immunohistochemical analysis, as well as the association of TAMs and AMC. RESULTS: We found that high CD68 or high CD163 expression was correlated with clinicopathological characteristics, high CD163 expression was an adverse predictor for both overall survival (OS) [hazard ratio (HR) = 2.265, P = 0.005] and progression- free survival (PFS) (HR = 1.925, P = 0.017) in patients with DLBCL. Patients with high CD68 or high CD163 expression had significantly poorer OS and PFS than those with low CD68 or low CD163 expression, respectively (CD68: OS: P<0.001, PFS: P<0.001; CD163: OS: P<0.001, PFS: P<0.001), even in the rituximab era. Moreover, high-risk patients could be further identified by the expression of CD68 or CD163, especially in those classified as low/intermediate risk by International Prognostic Index (IPI). Furthermore, the significant positive correlation was also detected between CD68 expression or CD163 expression and AMC (r = 0.256, P<0.001; r = 0.303, P<0.001). CONCLUSIONS: Patients with high expression of TAMs tend to have poorer OS and PFS, even in the rituximab era, and have positive correlation with AMC. Therefore, the peripheral AMC is a useful prognostic marker reflecting the status of the tumor microenvironment (TME) in DLBCL.

4.
Intern Med J ; 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31707755

RESUMO

BACKGROUND: H7N9 avian influenza is an infection of public health concern, in part because of its high mortality rate and pandemic potential. OBJECTIVES: We aimed to describe the clinical features of H7N9 avian influenza and the response to treatment. METHODS: Clinical, radiological, and histopathological data, and treatment-related of H7N9-infected patients hospitalized during 2014-2017 were extracted and analyzed. RESULTS: A total of 17 H7N9 patients (three females; mean age, 58.4 ± 13.7 years) were identified; of these six died. All patients presented with fever and productive cough; four patients had hemoptysis and 13 had chest distress and/or shortness of breath. Early subnormal white blood cell count and elevation of serum liver enzymes were common. Multilobar patchy shadows, rapid progression to ground-glass opacities, air bronchograms, and consolidation were the most common imaging findings. Histopathological examination of lung tissue of three patients who died showed severe alveolar epithelial cell damage, with inflammatory exudation into the alveolar space and hyaline membrane formation; widened alveolar septae, prominent inflammatory cell infiltration; and hyperplasia of pneumocytes. Viral inclusions were found in the lung tissue of two patients. All patients received antiviral drugs (oseltamivir ± peramivir). Four patients carried the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype, while the others had the C/T genotype. CONCLUSIONS: H7N9 virus infection causes human influenza-like symptoms, but may rapidly progress to severe pneumonia and even death. Clinicians should be alert to the possibility of H7N9 infection in high-risk patients. The presence of the IFITM3 rs12252-C genotype may predict severe illness. This article is protected by copyright. All rights reserved.

6.
Inorg Chem ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710211

RESUMO

The performance of MnII/III-monosubstituted heteropolytungstates [MnIII(H2O)GeW11O39]5- ([GT-MnIII-OH2]5-, where GT = GeW11O39) and [MnII(H2O)GeW11O39]6- ([GT-MnII-OH2]6-) as water oxidation catalysts at pH 9 was explored using density functional theory calculations. The counterion effect was fully considered, in which five and six Na+ ions were included in the calculations for water oxidation catalyzed by [GT-MnIII-OH2]5- and [GT-MnII-OH2]6-, respectively. The process of water oxidation catalysis was divided into three elemental stages: (i) oxidative activation, (ii) O-O bond formation, and (iii) O2 evolution. In the oxidative activation stage, two electrons and two protons are removed from [Na5-GT-MnIII-OH2] and three electrons and two protons are removed from [Na6-GT-MnII-OH2]. Therefore, the MnIV-O• species [Na5-GT-MnIV-O•] is obtained. Two mechanisms, (i) water nucleophilic attack and (ii) oxo-oxo coupling, were demonstrated to be competitive in O-O bond formation triggered from [Na5-GT-MnIV-O•]. In the last stage, the O2 molecule could be readily evolved from the peroxo or dinuclear species and the catalyst returns to the ground state after the coordination of a water molecule(s).

7.
J Nat Prod ; 82(11): 3065-3073, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31718182

RESUMO

Natural triterpenoids, such as oleanolic acid (OA) and hederagenin, display anti-lung cancer effects, and nitric oxide (NO) is associated with some oncogenic signaling pathways. Accordingly, 17 OA/hederagenin-NO donor hybrids were designed, synthesized, and evaluated against tumor cells. The most potent compound, 13, significantly inhibited the proliferation of five tumor cell lines (IC50 4.6-5.2 µM), while hederagenin inhibited the growth of only A549 tumor cells (IC50 > 10 µM). Furthermore, compound 13 showed stronger inhibitory effects on EGFR-LTC kinase activity (IC50 0.01 µM) than hederagenin (IC50 > 20 µM) and inhibited the proliferation of gefitinib-resistant H1975 (IC50 8.1 µM) and osimertinib-resistant H1975-LTC (IC50 7.6 µM) non-small-cell lung cancer (NSCLC) cells. Moreover, compound 13 produced the most NO in H1975 tumor cells, which indicated that NO may play a synergistic role. Collectively, compound 13, a novel hederagenin-NO donor hybrid with a different chemical structure from those of the current FDA-approved EGFR-targeted anti-NSCLC drugs, may be a promising lead compound for the treatment of NSCLC expressing gefitinib-resistant EGFR with a T790 M mutation or osimertinib-resistant EGFR-LTC with an L858R/T790M/C797S mutation. This work should shed light on the discovery of new anti-NSCLC drugs targeting EGFR from natural products.

8.
World J Gastroenterol ; 25(41): 6205-6221, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31749592

RESUMO

BACKGROUND: Chronic biliary obstruction results in ischemia and hypoxia of hepatocytes, and leads to apoptosis. Apoptosis is very important in regulating the homeostasis of the hepatobiliary system. Endoplasmic reticulum (ER) stress is one of the signaling pathways that induce apoptosis. Moreover, the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-induced apoptotic pathway is the main way; but its role in liver injury remains unclear. Yinchenhao decoction (YCHD) is a traditional Chinese medicine formula that alleviates liver injury and apoptosis, yet its mechanism is unknown. We undertook this study to investigate the effects of YCHD on the expression of ER stress proteins and hepatocyte apoptosis in rats with obstructive jaundice (OJ). AIM: To investigate whether YCHD can attenuate OJ-induced liver injury and hepatocyte apoptosis by inhibiting the PERK-CCAAT/enhancer-binding protein homologous protein (CHOP)-growth arrest and DNA damage-inducible protein 34 (GADD34) pathway and B cell lymphoma/leukemia-2 related X protein (Bax)/B cell lymphoma/leukemia-2 (Bcl-2) ratio. METHODS: For in vivo experiments, 30 rats were divided into three groups: control group, OJ model group, and YCHD-treated group. Blood was collected to detect the indicators of liver function, and liver tissues were used for histological analysis. For in vitro experiments, 30 rats were divided into three groups: G1, G2, and G3. The rats in group G1 had their bile duct exposed without ligation, the rats in group G2 underwent total bile duct ligation, and the rats in group G3 were given a gavage of YCHD. According to the serum pharmacology, serum was extracted and centrifuged from the rat blood to cultivate the BRL-3A cells. Terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling (TUNEL) assay was used to detect BRL-3A hepatocyte apoptosis. Alanine aminotransferase (ALT) and aspartate transaminase (AST) levels in the medium were detected. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to detect protein and gene expression levels of PERK, CHOP, GADD34, Bax, and Bcl-2 in the liver tissues and BRL-3A cells. RESULTS: Biochemical assays and haematoxylin and eosin staining suggested severe liver function injury and liver tissue structure damage in the OJ model group. The TUNEL assay showed that massive BRL-3A rat hepatocyte apoptosis was induced by OJ. Elevated ALT and AST levels in the medium also demonstrated that hepatocytes could be destroyed by OJ. Western blot or qRT-PCR analyses showed that the protein and mRNA expression levels of PERK, CHOP, and GADD34 were significantly increased both in the rat liver tissue and BRL-3A rat hepatocytes by OJ. The Bax and Bcl-2 levels were increased, and the Bax/Bcl-2 ratio was also increased. When YCHD was used, the PERK, CHOP, GADD34, and Bax levels quickly decreased, while the Bcl-2 levels increased, and the Bax/Bcl-2 ratio decreased. CONCLUSION: OJ-induced liver injury and hepatocyte apoptosis are associated with the activation of the PERK-CHOP-GADD34 pathway and increased Bax/Bcl-2 ratio. YCHD can attenuate these changes.

9.
Nat Commun ; 10(1): 5281, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754128

RESUMO

Supported noble metal nanoclusters and single-metal-site catalysts are inclined to aggregate into particles, driven by the high surface-to-volume ratio. Herein, we report a general method to atomically disperse noble metal nanoparticles. The activated carbon supported nanoparticles of Ru, Rh, Pd, Ag, Ir and Pt metals with loading up to 5 wt. % are completely dispersed by reacting with CH3I and CO mixture. The dispersive process of the Rh nanoparticle is investigated in depth as an example. The in-situ detected I• radicals and CO molecules are identified to promote the breakage of Rh-Rh bonds and the formation of mononuclear complexes. The isolated Rh mononuclear complexes are immobilized by the oxygen-containing functional groups based on the effective atomic number rule. The method also provides a general strategy for the development of single-metal-site catalysts for other applications.

10.
Sci Total Environ ; 701: 134515, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31734482

RESUMO

Tracking of reactive nitrogen (N) sources is important for the effective mitigation of N emissions. By combining the N and oxygen (O) isotopes of atmospheric NO3-, stable isotope mixing models were recently applied to evaluate the relative contributions of major NOx sources. However, it has long been unresolved how to accurately constrain the δ15N differences between NO3- and corresponding NOx (ε(NO2→NO3-) values). Here, we first incorporated the HC oxidation (NO2 → NO3-) pathway by using Δ17O values to evaluate the ε(NO2→NO3-) values, performed on NO3- in PM2.5 collected during the day and at night from January 4-13, 2015 at an urban site in Beijing. We found that the Δ17O-based ε values (ε17O-based(NO2→NO3-)) (15.6 ±â€¯7.4‰) differed distinctly from δ18O-based ε values (ε18O-based(NO2→NO3-)) (33.0 ±â€¯9.5‰) so did not properly incorporate the isotopic effects of the HC oxidation (NO2 → NO3-) pathway. Based on the ε(NO2→NO3-) values, δ15N values of NOx from coal combustion (CC), vehicle exhausts (VE), biomass burning (BB), and the microbial N cycle (MC), as well as NO3- in PM2.5, we further quantified the source contributions by using Stable Isotope Analysis in R (the SIAR model). We found that the respective fractional contributions of CC-NOx and MC-NOx were underestimated by 64% and were overestimated by 216% by using ε18O-based(NO2→NO3-) values. We concluded that the new ε17O-based(NO2→NO3-) values reduced uncertainties in contribution analysis and the evaluation method for atmospheric NO3- sources.

11.
Nat Prod Res ; : 1-8, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746227

RESUMO

Two new phenylpropanoids, named (2'R*,3'R*)-2',3'-dihydroxy-4'-methoxy-caffeoyl butyrate (1), 9-acetoxy syringin (2), and a new dihydrostilbene, named (8'R)-4',5-dihydroxy-4,8'-dimethoxy-2-hydroxyethyl diphenylethane (3), together with five analogues (4-8), were isolated from the flower buds of Magnolia biondii Pamp. Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. The absolute configurations were deduced by comparison of experimental and calculated gauge-independent atomic orbital (GIAO) 1 D NMR data. Moreover, the isolated compounds (1-8) were evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activities.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31746626

RESUMO

Maternal high fat diet (HFD) is associated with metabolic syndrome and cardiovascular diseases in adult offspring. Our previous study demonstrated that maternal HFD enhances pressor responses to angiotensin (ANG) II or a proinflammatory cytokine (PIC), which is associated with increased expression of brain renin-angiotensin system (RAS) components and PICs in adult offspring. The present study further investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) blocks sensitization of ANG II hypertension in offspring of HFD dams. All offspring were bred from dams with normal fat diet (NFD) or HFD starting two weeks prior to mating and maintained until weaning of the offspring. Then the weaned offspring were treated with an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water through the end of testing with a slow-pressor dose of ANG II. RT-PCR analyses of the lamina terminalis (LT) and paraventricular nucleus (PVN) revealed upregulation of mRNA expression of several RAS components and PICs in male offspring of HFD dams when compared to age-matched offspring of NFD dams. The enhanced gene expression was attenuated by blockade of either RAS or PICs. Likewise, ANG II administration produced an augmented pressor response in offspring of HFD dams. This was abolished by either ACE or TNF-α inhibitor. Taken together, this study provides mechanistic evidence and a therapeutic strategy that systemic inhibition of the RAS and PICs can block maternal HFD-induced sensitization of ANG II hypertension, which is associated with attenuation of brain RAS and PIC expression in offspring.

13.
Nat Prod Res ; : 1-8, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680553

RESUMO

Two new norsesquiterpenoids, dioscopposin A (1) and dioscopposin B (2), as well as 21 known compounds (3-23) were isolated from the stems and leaves of Dioscorea oppositifolia L. Their structures were elucidated by detailed analysis of comprehensive spectroscopic data. The absolute configurations were deduced by the comparison of experimental and calculated electronic circular dichroism spectra. Estrogenic activity of all the isolated compounds were evaluated using MCF-7 cells proliferation assay and compounds 2, 3, 7, 13, 15, 16, 18 and 21 exhibited proliferation activity.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31682318

RESUMO

CD20-positive T-cell lymphoma (TCL) is a very rare disease entity that is associated with the co-expressions of a range of T cell lineage makers, such as, CD2, CD3, CD5, or CD7, and CD20. The biological and clinical significance of CD20 antigen expressed in TCL has been unclear. Here, we are reporting an unusual case of CD20-positive primary nasal peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in a 62-year-old female with both peripheral blood (PB) and bone marrow (BM) involvement. Flow cytometry (FC) analysis revealed CD20+ lymphoma cells in PB, BM, and lymph node (LN) and was consistent with pathological findings. FC immunophenotyping was proved of great diagnostic contribution.

15.
Nanoscale ; 11(45): 22108-22117, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31720641

RESUMO

Biomimetic strategies have successfully been applied to confine multiple enzymes on scaffolds to obtain higher catalytic efficiency of enzyme cascades than freely distributed enzymes. However, the origin of high efficiency is poorly understood. We developed a coarse-grained, particle-based model to understand the origin of high efficiency. We found that a reaction intermediate is the key in affecting reaction kinetics. In the case of unstable intermediates, the confinement of multiple enzymes in clusters enhanced the catalytic efficiency and a shorter distance between enzymes resulted in a higher reaction rate and yield. This understanding was verified by co-encapsulating multiple enzymes in metal-organic framework (MOF) nanocrystals as artificially confined multienzyme complexes. The activity enhancement of multiple enzymes in MOFs depended on the distance between enzymes, when the decay of intermediates existed. The finding of this study is useful for designing in vitro synthetic biology systems based on artificial multienzyme complexes.

16.
Sci Rep ; 9(1): 17006, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740693

RESUMO

'Quality evaluation based on color grading' is one of the features used in Chinese medicine discrimination. In order to assess the feasibility of electronic eye (E-eye) in implementing 'quality evaluation based on color grading', the present study applied an IRIS VA400 E-eye to test 58 batches of Corni Fructus samples. Their optical data were acquired and combined with their corresponding classes. A total of four quality discrimination models were produced according to discrimination analysis (DA), least squares support vector machine (LS-SVM), partial least squares-discrimination analysis (PLS-DA), and principal component analysis-discrimination analysis (PCA-DA). The accuracy rate of the aforementioned 4 cross evaluation models were 86.21%, 89.66%, 81.03% and 91.38%, respectively. Therefore, the PCA-DA method was used to build the final discrimination model for classifying Corni Fructus or discriminating its quality.

17.
Int J Biol Macromol ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31726167

RESUMO

The occurrence of Maillard reaction in protein - polysaccharide coacervated microcapsules and its effects on microcapsule properties were investigated. Vitamin E microcapsules were prepared by soybean protein isolate - chitosan coacervation at 50 °C, 70 °C, or 90 °C for 12 h in the presence of maltose. Chromatic and furosine measurements revealed that Maillard reaction occurred in the microcapsules and was favored by high incubation temperatures. The three coacervation temperatures did not destroy the microcapsule structure, but improved the microencapsulation efficiency and microencapsulation yield instead. The microcapsules exhibited decreased aggregation and the increased absolute zeta potential and particle size were believed contribute to this improvement. Stability analysis demonstrated that the microcapsules possessed enhanced resistance to dissolution in water and improved storage stability than control microcapsules. It is concluded that coacervation at a temperature high enough to initiate Maillard reaction is a promising way to improve the physiochemical properties of protein - polysaccharide coacervated microcapsules.

18.
Clin Epigenetics ; 11(1): 153, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666131

RESUMO

PURPOSE: One major reason of the high mortality of epithelial ovarian cancer (EOC) is due to platinum-based chemotherapy resistance. Aberrant DNA methylation may be a potential mechanism underlying the development of platinum resistance in EOC. The purpose of this study is to discover potential aberrant DNA methylation that contributes to drug resistance. METHODS: By initially screening of 16 platinum-sensitive/resistant samples from EOC patients with reduced representation bisulfite sequencing (RRBS), the upstream region of the hMSH2 gene was discovered hypermethylated in the platinum-resistant group. The effect of hMSH2 methylation on the cellular response to cisplatin was explored by demethylation and knockdown assays in ovarian cancer cell line A2780. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was employed to examine the methylation levels of hMSH2 upstream region in additional 40 EOC patient samples. RT-qPCR and IHC assay was used to detect the hMSH2 mRNA and protein expression in extended 150 patients. RESULTS: RRBS assay discovered an upstream region from - 1193 to - 1125 of hMSH2 was significant hypermethylated in resistant EOC patients (P = 1.06 × 10-14). In vitro analysis demonstrated that global demethylation increased cisplatin sensitivity along with a higher expression of the hMSH2 mRNA and protein. Knockdown hMSH2 reduced the cell sensitivity to cisplatin. MALDI-TOF mass spectrometry assay validated the strong association of hypermethylation of hMSH2 upstream region with platinum resistance. Spearman's correlation analysis revealed a significantly negative connection between methylation level of hMSH2 upstream region and its expression. The Kaplan-Meier analyses showed the high methylation of hMSH2 promoter region, and its low expressions are associated with worse survival. In multivariable models, hMSH2 low expression was an independent factor predicting poor outcome (P = 0.03, HR = 1.91, 95%CI = 1.85-2.31). CONCLUSION: The hypermethylation of hMSH2 upstream region is associated with platinum resistant in EOC, and low expression of hMSH2 may be an index for the poor prognosis.

19.
EBioMedicine ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31761620

RESUMO

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer (EOC) with distinct pathological, biological, and molecular features. OCCCs are more resistant to conventional treatment regimen of EOC and have the worst stage-adjusted prognosis amongst EOC subtypes. As the OCCC incidence rate in Asian populations has significantly increased in recent decades, it is critical to elucidate its molecular features that could lead to OCCC-tailored therapeutic strategies. METHODS: Gene expression profiles of 222 OCCC were analyzed by hierarchical clustering and statistical analyses. FINDINGS: We identified two OCCC gene expression subtypes: EpiCC-epithelial-like, which is associated with early-stage disease, with a relatively higher rate of gene mutations in the SWI/SNF complex; and MesCC-mesenchymal-like, associated with late-stage and higher enrichment of immune-related pathway activity. Genetic, copy number and transcriptomic analyses showed that both EpiCC and MesCC carried OCCC-associated aberrations. The EpiCC/MesCC classification was reproducible in validation cohorts and OCCC cell lines. MesCC tumors had a poorer progression-free survival (PFS) than EpiCC tumors (HR: 3·0, p = 0·0006). Functional assays in cell lines showed that the MesCC subtype was more proliferative and more anoikis-resistant than the EpiCC. By applying the EpiCC/MesCC classification to the TCGA renal clear cell carcinoma cohort, our results indicated interoperability of the subtyping scheme, and revealed preferential drug response of MesCC to bevacizumab. INTERPRETATION: The EpiCC/MesCC classification shows promise for prognostic and therapeutic stratification in OCCC patients and warrants further investigation in the context of OCCC gene expression subtype-tailored treatment strategies.

20.
Plast Reconstr Surg ; 144(6): 1417-1428, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31764662

RESUMO

BACKGROUND: Computer-assisted mandibular reconstruction facilitates preoperative surgery simulation and transfers the virtual plan to a real operation. This systematic review and meta-analysis aimed to compare the accuracy, efficiency, postoperative complications, and economic viability between computer-assisted mandibular reconstruction and conventional freehand mandibular reconstruction. METHODS: The PubMed, Embase, Cochrane Library, and Google Scholar databases were searched up to November of 2018. The accuracy, efficiency, postoperative complications, and economic viability of computer-assisted mandibular reconstruction compared to conventional freehand mandibular reconstruction were systematically reviewed. Continuous and dichotomous data were pooled in mean difference (or standardized mean difference if necessary) and odds ratio, subsequently, with 95 percent confidence interval. RESULTS: A total of 12 studies were included in the systematic review, and data extracted from 11 of them were combined in meta-analysis. The accuracy of computer-assisted mandibular reconstruction was better than or equal to that of conventional freehand mandibular reconstruction according to qualitative analysis, although the quantitative comparison from meta-analysis was excluded because of the diversity of measurements. As for efficiency, computer-assisted mandibular reconstruction, when compared to conventional freehand mandibular reconstruction, revealed a shorter ischemic time, reconstructive time, total operative time, and length of stay. There was no difference in postoperative complication rate. CONCLUSIONS: Computer-assisted mandibular reconstruction showed increased efficiency considering the reduced ischemic time, total operative time, reconstructive time, and length of stay. However, the accuracy, reconstruction outcomes, and perioperative cost should be further elucidated because of diverse measurements and the lack of included studies.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA