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1.
Invest Ophthalmol Vis Sci ; 60(14): 4583-4595, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675075

RESUMO

Purpose: Trabecular meshwork (TM) cells detect and coordinate responses to intraocular pressure (IOP) in the eye. TM cells become dysfunctional in glaucoma where IOP is often elevated. Recently, we showed that normal TM (NTM) cells communicate by forming tubular connections called tunneling nanotubes (TNTs). Here, we investigated TNTs in glaucomatous TM (GTM) cells. Methods: Primary GTM and NTM cells were established from cadaver eyes. Transfer of Vybrant DiO and DiD-labeled vesicles via TNT connections was measured. Imaris software measured the number and length of cell protrusions from immunofluorescent confocal images. Live-cell imaging of the actin cytoskeleton was performed. The distribution of myosin-X, a regulator of TNTs/filopodia, was investigated in TM cells and tissue. Results: GTM cells contained significantly more transferred fluorescent vesicles than NTM cells (49.6% vs. 35%). Although NTM cells had more protrusions at the cell surface than GTM cells (7.61 vs. 4.65 protrusions/cell), GTM protrusions were significantly longer (12.1 µm vs. 9.76 µm). Live-cell imaging demonstrated that the GTM actin cytoskeleton was less dynamic, and vesicle transfer between cells was significantly slower than NTM cells. Furthermore, rearrangement of the actin cortex adjacent to the TNT may influence TNT formation. Myosin-X immunostaining was punctate and disorganized in GTM cells and tissue compared to age-matched NTM controls. Conclusions: Together, our data demonstrate that GTM cells have phenotypic and functional differences in their TNTs. Significantly slower vesicle transfer via TNTs in GTM cells may delay the timely propagation of cellular signals when pressures become elevated in glaucoma.

2.
Int J Biochem Cell Biol ; : 105639, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31669139

RESUMO

The main event in the progression of pulmonary fibrosis is the appearance of myofibroblasts. Recent evidence supports pericytes as a major source of myofibroblasts. TGFß/Smad2/3 and PDGF/Erk signaling pathways are important for regulating pericyte activation. Previous studies have demonstrated that PDGFßR and TGFßR are modified by core fucosylation (CF) catalyzed by α-1,6-fucosyltransferase (FUT8). The aim of this study was to compare the effect of inhibiting CF versus the PDGFßR and TGFßR signaling pathways on pericyte activation and lung fibrosis. FUT8shRNA was used to knock down FUT8-mediated CF both in vivo and in isolated lung pericytes. The small molecule receptor antagonists, ST1571 (imatinib) and LY2109761, were used to block the PDGFß/pErk and TGFß/pSmad2/3 signaling pathways, respectively. Pericyte detachment and myofibroblastic transformation were assessed by immunofluorescence and Western blot. Histochemical and immunohistochemical staining were used to evaluate the effect of the intervention on pulmonary fibrosis. Our findings demonstrate that FUT8shRNA significantly blocked pericyte activation and the progression of pulmonary fibrosis, achieving intervention effects superior to the small molecule inhibitors. The PDGFß and TGFß pathways were simultaneously affected by the CF blockade. FUT8 expression was upregulated with the transformation of pericytes into myofibroblasts, and silencing FUT8 expression inhibited this transformation. In addition, there is a causal relationship between CF modification catalyzed by FUT8 and pulmonary fibrosis. Our findings suggest that FUT8 may be a novel therapeutic target for pulmonary fibrosis.

3.
Int J Methods Psychiatr Res ; : e1803, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31568624

RESUMO

OBJECTIVES: A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum. METHODS: Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics. RESULTS: Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased. CONCLUSION: Different interviews may not classify major depression equivalently.

4.
Psychother Psychosom ; : 1-13, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593971

RESUMO

BACKGROUND: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results. OBJECTIVE: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10. METHODS: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview. RESULTS: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88). CONCLUSIONS: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.

5.
Int J Rheum Dis ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595672

RESUMO

AIM: In patients with Takayasu's arteritis (TA), current biomarkers that properly reflect the progression of the vascular structure remain absent. We aimed to determine the serum leptin level to investigate its relationship with imaging changes and assess its value as a predictor for long-term radiological progression. METHOD: This study included 34 untreated TA patients and 40 age-matched healthy controls. At baseline and during the 5-year follow-up, we assessed disease activity using Kerr's criteria and Indian Takayasu Clinical Activity Score (ITAS2010) and monitored laboratory biomarkers as well as imaging findings. Serum leptin levels were measured by enzyme-linked immunosorbent assay. RESULTS: The baseline serum leptin levels were significantly higher in TA patients than in healthy controls. Leptin was significantly positively correlated with triglyceride and high-density lipoprotein cholesterol levels and negatively correlated with fibrinogen and C-reactive protein levels. Patients were subdivided into three groups based on their baseline leptin level. During a 5-year follow-up, patients in the high and medium leptin groups showed more radiological progression compared to those in the low leptin group. Cox proportional hazard regression analysis showed that a high serum leptin level was a positive predictor of radiological progression. CONCLUSION: Leptin is a potential biomarker for assessing TA structural progression. Untreated patients with elevated serum leptin levels are at a higher risk of progression in the aorta. Thus, the leptin level can be a predictor of long-term radiological progression.

6.
Life Sci ; 236: 116899, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614145

RESUMO

AIMS: The aim of our study is to illustrate the role of amphiregulin in trophoblast invasiveness and underlying signal cascades. MAIN METHODS: An immortalized human early extravillous cell line, HTR-8/SVneo, was used for this investigation. Matrigel-transwell invasion assay was used for testing the effects of amphiregulin on cell invasiveness. MMP9 and MMP2 mRNA expression level and activity were measured using Rt-qPCR and zymographic analysis. Cell signals involved in the invasion process were verified using western blot and specific inhibitors. KEY FINDINGS: Our results showed that amphiregulin could promote HTR-8/SVneo cell invasiveness without interfering cell proliferation, and significantly upregulate the expression of MMP9 and TIMP-1 mRNAs as well as the ratio of MMP9/TIMP-1. Using specific inhibitors for MEK and PI3K signaling further indicated that, both ERK1/2 and Akt signal pathways were required for amphiregulin-induced cell invasiveness. The co-ordination between ERK1/2 and Akt signaling pathway was needed for the upregulation of MMP9 mRNA, while ERK1/2 was more essential for the upregulation of TIMP-1 mRNA. Meanwhile, we first put forward that the deficiency of amphiregulin expression in trophoblast might be compensated by the upregulation of epidermal growth factor receptor (EGFR) and heparin-binding EGF (HB-EGF) mRNA. SIGNIFICANCE: ERK1/2 and Akt signaling pathways mediate amphiregulin-induced upregulation of MMP9 mRNA and the MMP9/TIMP-1 ratio, which subsequently contribute to amphiregulin-promotion of HTR-8/SVneo cell invasion.

7.
J Mater Chem B ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31625545

RESUMO

The transgelin-2 (TAGLN2) protein plays an important role in multidrug resistance in human breast cancer. siRNA mediated gene silencing of TAGLN2 is a promising strategy for paclitaxel resistance reversal in breast cancer. In this study, a series of bioreducible and acid-labile polydiethylenetriamines (PDs) with different proportions of cross-linkers were synthesized. TAGLN2 siRNA was condensed by PDs to form dual-responsive nanocomplexes, and these nanocomplexes were hypothesized to partially degrade in the acidic environment of endosomes, and then completely degrade in the reducing environment of the cytoplasm to release siRNA. It was found that PDs have good water solubility, acid-base buffering capacity, suitable degradability and high biocompatibility. Moreover, PDCKM can deliver TAGLN2 siRNA into MCF-7/PTX cells and inhibit the expression of TAGLN2 even better than PEI 25k. Besides, paclitaxel showed higher cytotoxicity in cells incubated with PDCKM/TAGLN2 siRNA nanocomplexes. These results suggested that PDs have great potential for safe and efficient siRNA delivery to reverse paclitaxel resistance in breast cancer.

8.
Aging (Albany NY) ; 112019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619582

RESUMO

Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in ovarian steroidogenesis and progesterone (P4) synthesis. Melatonin and its receptors are expressed in human granulosa cells, and have been shown to influence basal P4 production. However, previous studies addressing the regulation of StAR expression by melatonin and its impact on P4 secretion yielded contradictory results. Here, we demonstrate that melatonin upregulates StAR expression in primary cultures of human granulosa-lutein (hGL) cells obtained from women undergoing in vitro fertilization (IVF). Using pharmacological inhibitors, we show that the stimulatory effect of melatonin on StAR expression is mediated via both MT1 and MT2 melatonin receptors. Melatonin exposure activates the PI3K/AKT signaling pathway and its inhibition attenuates the stimulatory effect of melatonin on StAR expression. Moreover, siRNA-mediated knockdown of StAR abolishes melatonin-induced P4 production. Importantly, clinical analyses demonstrate that melatonin levels in human follicular fluid are positively correlated with P4 levels in serum. By illustrating the potential physiological role of melatonin in the regulation of StAR expression and P4 production in hGL cells, our results may serve to improve current strategies used to treat clinical infertility.

10.
Plant J ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659806

RESUMO

The CO2 transfer conductance within plant leaves (mesophyll conductance, gm ) is currently not considered explicitly in most land surface models (LSMs), but instead treated implicitly as an intrinsic property of the photosynthetic machinery. Here, we review approaches to overcome this model deficiency by explicitly accounting for gm , which comprises the re-adjustment of photosynthetic parameters and a model describing the variation of gm in dependence of environmental conditions. An explicit representation of gm causes changes in the response of photosynthesis to environmental factors, foremost leaf temperature and ambient CO2 concentration, which are most pronounced when gm is small. These changes in leaf-level photosynthesis translate into a stronger climate and CO2 response of gross primary productivity (GPP) and transpiration at the global scale. The results from two independent studies show consistent latitudinal patterns of these effects with biggest differences in GPP in the boreal zone (up to ~15%). Transpiration and evapotranspiration show spatially similar, but attenuated, changes compared to GPP. These changes are indirect effects of gm caused by the assumed strong coupling between stomatal conductance and photosynthesis in current LSMs. Key uncertainties in these simulations are the variation of gm with light and the robustness of its temperature response across plant types and growth conditions. Future research activities focusing on the response of gm to environmental factors and its relation to other plant traits have the potential to improve the representation of photosynthesis in LSMs and to better understand its present and future role in the Earth system.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 226: 117544, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31629982

RESUMO

We designed and synthesized a water-soluble near-infrared (NIR) fluorescent probe with the recognition unit of the cyanine-like structure and acrylate group. Through an aromatic ring nucleophilic substitution reaction based on sulfhydryl moiety, an off-on fluorescence response toward cysteine (Cys) was realized. The probe exhibited excellent spectral performance with an emission wavelength of 720 nm and a detection limit of 0.20 µM. The spectral properties, selectivity and anti-interference performance of the probe were systematically investigated. Density functional theory (DFT) calculations were conducted to clarify the luminescence mechanism of the probe. Furthermore, the probe was successfully applied to the detection of free Cys in human serum and the NIR imaging of endogenous Cys in living cells. Thus, the probe has a promising application prospect in clinical diagnosis and fluorescence imaging.

12.
BMC Med ; 17(1): 190, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31640711

RESUMO

BACKGROUND: In locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone. METHODS: All patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959, n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts. RESULTS: Three imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25-0.74, p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (pinteraction <  0.001). This trend was also found in the validation cohort with high (n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06-0.51, p <  0.001) and low ICTOS (n = 175, p = 0.31), with a significant treatment interaction (pinteraction = 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors. CONCLUSION: An imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01245959 . Registered 23 November 2010.

13.
Mil Med Res ; 6(1): 32, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31651361

RESUMO

Locally recurrent head and neck squamous cell carcinoma (HNSCC) is often unresectable, and a repeat course of radiotherapy is associated with incremental toxicities. Boron neutron capture therapy (BNCT) is a novel targeted radiotherapy modality that can achieve a high dose gradient between cancerous and adjacent normal tissues. However, the relationships among the dose resulting from BNCT, tumor response to BNCT, and survival are not completely understood. Recently, a study published in Radiotherapy and Oncology investigated the efficacy of BNCT in the treatment of patients with locally recurrent HNSCC and the factors associated with favorable treatment response and survival. In this article, the findings, strengths and limitations of this study are discussed in depth, and the significance of the study and motivations for future research are highlighted.

14.
Br J Radiol ; : 20181055, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31596129

RESUMO

OBJECTIVE: We proposed to determine whether the performance of inexperienced radiologists in determining extramural vascular invasion (EMVI) in rectal cancer on MRI can be promoted by means of targeted training. METHODS: 230 rectal cancer patients who underwent pre-operative chemoradiotherapy were included. Pre-therapy and post-therapy MR images and pathology EMVI evaluation were available for cases. 230 cases were randomly divided into 150 training cases and 80 testing cases, including 40 testing case A and 40 testing case B. Four radiologists were included for MRI EMVI evaluation, who were divided into targeted training group and non-targeted training group. The two groups evaluated testing case A at baseline, 3 month and 6 month, evaluated testing case B at 6 month. The main outcome was agreement with expert-reference for pre-therapy and post-therapy evaluation, the other outcome was accuracy with pathology for post-therapy evaluation. RESULTS: After 6 months of training, targeted training group showed statistically higher agreement with expert-reference than non-targeted training group for both pre-therapy and post-therapy MRI EMVI evaluation of testing case A and testing case B, all p < 0.05. Targeted training group also showed significantly higher accuracy with pathology than non-targeted training group for post-therapy evaluation of testing case A and testing case B after 6 months of training, all p < 0.05. CONCLUSION: The diagnostic performance for MRI EMVI evaluation could be promoted by targeted training for inexperienced radiologist. ADVANCES IN KNOWLEDGE: This study provided the first evidence that after 6 month targeted training, inexperienced radiologists demonstrated improved diagnostic performance, with a 20% increase in agreement with expert-reference for both pre-therapy and post-therapy MRI EMVI evaluation and also a 20% increase in or accuracy with pathology for post-therapy evaluation, while inexperienced radiologists could not gain obvious improvement in MRI EMVI evaluation through the same period of regular clinical practice. It indicated that targeted training may be necessary for helping inexperienced radiologist to acquire adequate experience for the MRI EMVI evaluation of rectal cancer, especially for radiologist who works in a medical unit where MRI EMVI diagnosis is uncommon.

15.
BMC Geriatr ; 19(1): 269, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615427

RESUMO

BACKGROUND: Acute infection leads to substantial mortality in the nonagenarian population. However, the predictive efficacies of functional status and biochemical indexes for in-hospital mortality in these patients remain to be determined. METHODS: A single-center, retrospective cohort study was performed. Consecutive nonagenarian patients who were admitted to our department from January 1, 2014 to December 31, 2016 for acute infectious diseases were included. Baseline data for medical history, functional status, and biochemical indexes were obtained on admission. The outcomes of these patients during hospitalization were recorded. Predictors of in-hospital mortality were identified via logistic regression analyses. RESULTS: A total of 162 patients were included, and 46 patients died (17.2%) during hospitalization. Univariate analysis showed that the prevalence rates of atrial fibrillation (32.1%) and malignant disease (26.5%) were higher in nonagenarian patients who died during hospitalization than in those who discharged. Multivariate logistic regression analyses identified malignant disease (odds ratio [OR] 2.73, 95% confidence interval [CI]: 1.10-6.78), ADL category (OR 0.82, 95% CI: 0.75-0.89) and serum albumin (OR 0.86, 95%CI 0.78-0.95) as independent predictors of in-hospital mortality in nonagenarian patients hospitalized for acute infection. CONCLUSIONS: Functional impairment as well as serum albumin may be independent predictors of in-hospital mortality in nonagenarian patients hospitalized for acute infectious diseases. Stratification of patients according to Barthel Index score and serum albumin is very necessary.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31664670

RESUMO

In this study, the quality of groundwater was tested in 95 sampling wells in Shuangliao City. Based on the results, the coefficient of variation method was used to calculate the comprehensively evaluated value F, and the grade of groundwater quality, in accordance with the actual scenario in the study area, was classified according to the results of the evaluation. The spatial distribution of groundwater quality types in the study area was classified. In addition, the influence of human activity on each groundwater subsystem was assessed. Combined with the land use types in the study area, the Circle model was used to extract the land use types in the circular buffer zone with a radius of 500 m, and the Kendall rank correlation test was used to analyze the influence of the land use types on the spatial distribution of groundwater pollution. Based on the coefficient of variation, the groundwater quality standard was divided into four sections considering the actual scenario: ≤ 0.92 (I), 0.92~≤ 1.75 (II), 1.75~≤ 2.40 (III), and > 2.40 (IV). Water from class II was considered the main type for groundwater quality. NO3-, TFe, and Mn were deemed the main indexes of groundwater pollution. Further, land use type was found to have a great influence on the spatial distribution of groundwater pollution; specifically, dry land, paddy field, areas with dense traffic, and residential areas are the main land types that affect the groundwater environment.

17.
Cell Death Dis ; 10(11): 800, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641108

RESUMO

Abnormal aggregation of misfolded pathological proteins in neurons is a prominent feature of neurodegenerative disorders including Parkinson's disease (PD). Perturbations of proteostasis at the endoplasmic reticulum (ER) triggers ER stress, activating the unfolded protein response (UPR). Chronic ER stress is thought to underlie the death of neurons during the neurodegenerative progression, but the precise mechanism by which the UPR pathways regulate neuronal cell fate remains incompletely understood. Here we report a critical neurodegenerative role for inositol-requiring enzyme 1 (IRE1), the evolutionarily conserved ER stress sensor, in a Drosophila model of PD. We found that IRE1 was hyperactivated upon accumulation of α-synuclein in the fly photoreceptor neurons. Ectopic overexpression of IRE1 was sufficient to trigger autophagy-dependent neuron death in an XBP1-independent, JNK-dependent manner. Furthermore, IRE1 was able to promote dopaminergic neuron loss, progressive locomotor impairment, and shorter lifespan, whereas blocking IRE1 or ATG7 expression remarkably ameliorated the progression of α-synuclein-caused Parkinson's disease. These results provide in vivo evidence demonstrating that the IRE1 pathway drives PD progression through coupling ER stress to autophagy-dependent neuron death.

18.
Eur Radiol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31650266

RESUMO

OBJECTIVES: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for nasopharyngeal carcinoma (NPC) merged T4N0-2 and T1-4N3 to create stage IVa. In the present study, we aimed to assess the difference in clinical outcomes and patterns of failure between 8th AJCC T4N0-2 and T1-4N3 NPC patients treated with intensity-modulated radiotherapy (IMRT). METHODS: We included 3107 patients with stage IVa NPC disease (1871 with T4N0-2 and 1236 with T1-4N3) according to the 8th AJCC staging system. Overall survival (OS) was the primary endpoint. The clinical outcomes between T4N0-2 and T1-4N3 patients were compared. RESULTS: T1-4N3 patients had significantly worse 3-year OS (84.1% vs. 89.2%; p < 0.001) and distant metastasis-free survival (DMFS; 78.3% vs. 85.9%; p < 0.001), but better local relapse-free survival (LRFS; 94.9% vs. 92.2%; p = 0.003), as compared with T4N0-2 patients. Multivariate analysis showed that T1-4N3 was still an independent adverse prognostic factor for both DMFS (hazard ratio [HR] = 1.517, 95% confidence interval [CI] = 1.274-1.806, p < 0.001) and OS (HR = 1.315, 95% CI = 1.100-1.572, p = 0.003), whereas T4N0-2 was an independent adverse prognostic factor for LRFS (HR = 1.581, 95% CI = 1.158-2.158, p = 0.004). CONCLUSIONS: In terms of the OS, T4N0-2 patients had better prognosis compared with T1-4N3 patients, and the patterns of failure differed between T4N0-2 and T1-4N3 patients. We believe that future modifications of the AJCC/UICC staging system should separate T4N0-2 from T1-4N3. KEY POINTS: • In nasopharyngeal carcinoma, T4N0-2 patients tended to develop local relapse, whereas T1-4N3 patients were more likely to develop distant metastasis. • In terms of overall survival, T4N0-2 patients had better prognosis than T1-4N3 patients. • T4N0-2 should be separated from T1-4N3 in the UICC/AJCC staging system.

19.
Langmuir ; 35(39): 12773-12781, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31498639

RESUMO

Inkjet printing of biopolymer droplets is gaining popularity because of its potential applications in regenerative medicine, particularly the fabrication of tissue-regenerative scaffolds. The quality of bioprinting, which affects cellular behaviors and the subsequent tissue formation, is determined by the solvent evaporation and deposition processes of biopolymer droplets, during which instantaneous local viscosity and surface tension changes occur because of the redistribution of the biopolymer inside the drop. Such dynamics is complex and not well understood. Most biopolymer inks also contain multiple solvents of distinct evaporation rates, further complicating the system dynamics. Using high-speed interferometry, we directly observe in real time the instantaneous drop shape of inkjet-printed picoliter gelatin drops containing glycerol and water. It is observed that, for bisolvent gelatin drops with surfactants, highly viscous gelatin and glycerol accumulated near the pinned contact line at an early stage suppress the evaporation-driven outward flow and create a stagnation zone near the contact line region. Lower surface tension at the contact line, because of its high local surfactant concentration, as compared to the drop apex induces a strong Marangoni recirculation, which in conjunction with a stagnation zone in the contact line region causes the instantaneous drop shape to transition from a spherical cap to a volcano shape during evaporation and resulting in a volcano-like deposition profile. In contrast, the suppressed evaporation outward flow together with a weak Marangoni flow leads to a domelike deposition for the case without surfactant. The role of surfactant in polymer drop deposition with water-only solvent is also investigated and compared against that of bisolvent drops. For the single-solvent case, the deposition profile is found to shift from a coffee-eye shape in the presence of surfactant to a uniform deposition without surfactant. The results reveal new insight into the complex role surfactant plays during polymer drop evaporation and deposition processes.

20.
Sheng Wu Gong Cheng Xue Bao ; 35(9): 1723-1735, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31559754

RESUMO

To establish a quantitative ELISA for human interleukin-35 (IL-35) detection, we cloned cDNAs encoding the 2 subunits IL-27EBI3 and IL-12p35 of IL-35 by RT-PCR and transformed the cDNAs into Escherichia coli BL21 star (DE3) by recombinant DNA technology. IL-27EBI3 and IL-12p35 were expressed as recombinant proteins and used as immunogen to immunize Balb/c mice. Spleen cells from the positive serum mice were isolated and fused with SP-2/0 myeloma cells. We obtained the hybridoma cell lines stably secreting target antibodies by indirect ELISA screening of the cell supernatants with recombinant IL-27EBI3 and IL-12p35 as antigen and consecutive subcloning of the cells in the well with positive supernatant. Following further measurement of supernatant titers of the antibodies and identification of their antigen specificity, we obtained a hybridoma cell line 3B11 that stably secrets antibody against IL-27EBI3 and a hybridoma cell line 3A10 that secrets antibody against IL-12p35. Both monoclonal antibodies (mAbs) were identified as the subtype of IgG1. Finally, using the anti-IL-27EBI3 mAb from 3B11 as the capture antibody and the anti-IL-12p35 mAb from 3A10 as the secondary antibody, we established a quantitative double-antibodies sandwich ELISA for IL-35 detection with streptavidin-biotin amplification system. Results demonstrated that the quantitative assay had a detection range of 3.12-200 pg/mL, a detectability of 1.26 pg/mL, and a crossing-reactive rate of 0.1%. The intra-batch RSD and the inter-batch RSD of the quantitative assay were 5.1%-5.6% and 5.6%-7.2%, respectively, and the fortified recovery was 89%-103%. Therefore, the sandwich ELISA assay for IL-35 meets the qualification of quantitative analysis and laid a stable foundation for the development of quantitative ELISA kit for IL-35 detection.


Assuntos
Ensaio de Imunoadsorção Enzimática , Animais , Anticorpos Monoclonais , Especificidade de Anticorpos , Humanos , Hibridomas , Interleucinas , Camundongos , Camundongos Endogâmicos BALB C
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