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1.
J Clin Pathol ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034058

RESUMO

AIMS: Gastric cancer is one of the leading causes for cancer mortality. Recent studies have defined the landscape of genomic alterations of gastric cancer and their association with clinical outcomes. However, the pathogenesis of gastric cancer has not been completely characterised. METHODS: Driver genes were detected by five computational tools, MutSigCV, OncodriveCLUST, OncodriveFM, dendrix and edriver, using mutation data of stomach adenocarcinoma (STAD) from the cancer genome altas database, followed by an integrative investigation. RESULTS: TTN, TP53, LRP1B, CSMD3, OBSCN, ARID1A, FAT4, FLG, PCLO and CSMD1 were the 10 most frequently mutated genes. PIK3CD, NLRC3, FMNL1, TRAF3IP3 and CR1 were the top five hub genes of the blue coexpression module positively correlated with pathological tumour stage and lymph node stage (p values <0.05 for all cases). Hierarchical clustering analysis of copy number variations of driver genes revealed three subgroups of STAD patients, and cluster 2 tumours were significantly associated with lower lymph node stage, less number of positive lymph nodes and higher microsatellite instability and better overall survival than cluster 1 and cluster 3 tumours (p values <0.05 for all cases, Wilcoxon rank-sum test or log rank test). High expression in one or more of DNER, LHCGR, NLRP14, OR4N2, PSG6, TTC29 and ZNF568 genes was associated with increased mortality (p values <0.05 for all cases, log rank test). CONCLUSIONS: The driver genes shed insights into the tumourigenesis of gastric cancer and the genes DNER, LHCGR, NLRP14, OR4N2, PSG6, TTC29 and ZNF568 pave the way for developing prognostic biomarkers for the disease.

3.
Viruses ; 12(2)2020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-32024281

RESUMO

Although seasonal influenza vaccines block most predominant influenza types and subtypes, humans still remain vulnerable to waves of seasonal and new potential pandemic influenza viruses for which no immunity may exist because of viral antigenic drift and/or shift. Previously, we described a human monoclonal antibody (hMAb), KPF1, which was produced in human embryonic kidney 293T cells (KPF1-HEK) with broad and potent neutralizing activity against H1N1 influenza A viruses (IAV) in vitro, and prophylactic and therapeutic activities in vivo. In this study, we produced hMAb KPF1 in tobacco plants (KPF1-Antx) and demonstrated how the plant-produced KPF1-Antx hMAb possesses similar biological activity compared with the mammalian-produced KPF1-HEK hMAb. KPF1-Antx hMAb showed broad binding to recombinant HA proteins and H1N1 IAV, including A/California/04/2009 (pH1N1) in vitro, which was comparable to that observed with KPF1-HEK hMAb. Importantly, prophylactic administration of KPF1-Antx hMAb to guinea pigs prevented pH1N1 infection and transmission in both prophylactic and therapeutic experiments, substantiating its clinical potential to prevent and treat H1N1 infections. Collectively, this study demonstrated, for the first time, a plant-produced influenza hMAb with in vitro and in vivo activity against influenza virus. Because of the many advantages of plant-produced hMAbs, such as rapid batch production, low cost, and the absence of mammalian cell products, they represent an alternative strategy for the production of immunotherapeutics for the treatment of influenza viral infections, including emerging seasonal and/or pandemic strains.

4.
J Nutr ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027752

RESUMO

BACKGROUND: Probiotic Lactobacillius rhamnosus GG (LGG) shows beneficial immunomodulation on cultured cell lines in vitro and in mouse models. OBJECTIVE: The aim was to investigate the effects of LGG on intestinal injury and the underlying mechanisms by elucidating inflammatory signaling pathways and metabolomic response to LPS stimulation in the piglet intestine. METHODS: Piglets (Duroc × Landrace × Large White, including males and female; 8.6 ± 1.1 kg) aged 28 d were assigned to 3 groups (n = 6/group): oral inoculation with PBS for 2 wk before intraperitoneal injection of physiological saline [control (CON)] or LPS (25 µg/kg body weight; LPS) or oral inoculation with LGG for 2 wk before intraperitoneal injection of LPS (LGG+LPS). Piglets were killed 4 h after LPS injection. Systemic inflammation, intestinal integrity, inflammation signals, and metabolomic characteristics in the intestine were determined. RESULTS: Compared with CON, LPS stimulation significantly decreased ileal zonula occludens 1 (ZO-1; 44%), claudin-3 (44%), and occludin (41%) expression; increased serum diamineoxidase (73%), D-xylose (19%), TNF-α (43%), and IL-6 (55%) concentrations; induced p38 mitogen-activated protein kinase (p38 MAPK; 85%), extracellular signal-regulated kinase (ERK; 96%), and NF-κB p65 phosphorylation (37%) (P < 0.05). Compared with LPS stimulation alone, LGG pretreatment significantly enhanced the intestinal barrier by upregulating expressions of tight junction proteins (ZO-1, 73%; claudin-3, 55%; occludin, 67%), thereby decreasing serum diamineoxidase (26%) and D-xylose (28%) concentrations, and also reduced serum TNF-α expression (16%) and ileal p38 MAPK (79%), ERK (43%) and NF-κB p65 (37%) phosphorylation levels (P < 0.05). Metabolomic analysis showed clear separation between each group. The concentrations of caprylic acid [fold-change (FC) = 2.39], 1-mono-olein (FC = 2.68), erythritol (FC = 4.62), and ethanolamine (FC = 4.47) significantly increased in the intestine of LGG + LPS piglets compared with the LPS group (P < 0.05). CONCLUSIONS: These data suggest that LGG alleviates gut inflammation, improves intestinal barrier function, and modulates the metabolite profile of piglets challenged with LPS. This trial was registered at the Zhejiang University (http://www.lac.zju.edu.cn) as ZJU20170529.

5.
Phys Chem Chem Phys ; 22(3): 1721-1726, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31895354

RESUMO

Subnano-clusters are commonly the important active components on many catalysts in heterogeneous catalysis and finding an effective structural descriptor is key to designing new catalysts. However, the progress of obtaining such a descriptor falls far-short of expectation due to their well-known complicated structures. Herein, we propose a function of sigmoid coordination number (f(SCN)) as a structural descriptor, and develop an explicit equation to predict adsorption energies on CenO2n (n = 1-10) subnano-clusters using H adsorption as an example because of the importance of (de)hydrogenation in heterogeneous catalysis. We show an excellent linear correlation between H-adsorption energies and f(SCN) with RMSE = 0.05 eV and R2 = 0.97. The generality of this equation is also verified using other different sizes CenO2n (n = 12-14) subnano-clusters with RMSE = 0.02 eV. We demonstrate that the structural descriptor not only provides an excellent quantitative structure-reactivity relationship for metal oxide clusters, but also deepens the understanding of structure-reactivity relationship, which may have far-reaching implications in heterogeneous catalysis.

7.
PLoS One ; 15(1): e0227770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945111

RESUMO

Blood flow in an artery is a fluid-structure interaction problem. It is widely accepted that aneurysm formation, enlargement and failure are associated with wall shear stress (WSS) which is exerted by flowing blood on the aneurysmal wall. To date, the combined effect of aneurysm size and wall elasticity on intra-aneurysm (IA) flow characteristics, particularly in the case of side-wall aneurysms, is poorly understood. Here we propose a model of three-dimensional viscous flow in a compliant artery containing an aneurysm by employing the immersed boundary-lattice Boltzmann-finite element method. This model allows to adequately account for the elastic deformation of both the blood vessel and aneurysm walls. Using this model, we perform a detailed investigation of the flow through aneurysm under different conditions with a focus on the parameters which may influence the wall shear stress. Most importantly, it is shown in this work that the use of flow velocity as a proxy for wall shear stress is well justified only in those sections of the vessel which are close to the ideal cylindrical geometry. Within the aneurysm domain, however, the correlation between wall shear stress and flow velocity is largely lost due to the complexity of the geometry and the resulting flow pattern. Moreover, the correlations weaken further with the phase shift between flow velocity and transmural pressure. These findings have important implications for medical applications since wall shear stress is believed to play a crucial role in aneurysm rupture.

8.
Phytochemistry ; 171: 112228, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31911265

RESUMO

A previously undescribed taraxerene-type triterpenoid possessing a class of rare natural taraxerene triterpenoid possessing skeleton with 14, 28-lactone, two undescribed oleane-type triterpenoids, and twenty-five known triterpenoids were isolated from Liquidambar formosana (Hamamelidaceae). The structures of undescribed compounds were determined on the basis of 1D and 2D NMR spectroscopic, HR-ESI-MS, and X-ray crystallographic data analysis. Among the isolates, ursolic acid, 3,6-dion-20(29)-lupen-28-oic acid, and 3-oxo-12α-hydroxyoleanan-28,13ß-olide induced a significant apoptosis in SMMC7721 cells in the flow cytometer experiment with apoptosis rates of 94.5%, 57.3% and 89.9% at 8.0 µM, respectively, exhibiting near equivalent apoptosis-inducing abilities to that positive drug taxol (apoptotic rate of 71.2% at 1.4 µM). Mechanism studies suggested that these three compounds could regulate the mitochondrial pathway by up-regulating the expressions of pro-apoptotic factors (Bad and Bax) and activating caspase-3 and caspase-9 to induce apoptosis. Further studies indicated that the pro-apoptotic effects of these three compounds were associated with PI3K-AKT pathway inhibition. Taken together, these studies provide evidence that triterpenoids from L. Fructus are promising candidates for the hepatocellular carcinoma therapy.

9.
Biochem Biophys Res Commun ; 523(2): 527-534, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31924304

RESUMO

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the world, and is tightly associated with microglia-regulated neuroinflammation. However, the activation profile of microglia during the pathophysiological responses is still not fully understood. Micro-RNAs (miRs), as noncoding RNAs, are involved in the progression of TBI. In this study, we attempted to explore the effects of miR-193a on TBI using the in vivo and in vitro studies. Following experimental TBI in mice, we found that miR-193a expression was significantly up-regulated in ipsilateral cortical tissues and in the microglia/macrophages isolated from the ipsilateral cortical tissues, which was accompanied with markedly enhanced expression of pro-inflammatory factors. We then found that miR-193a hairpin inhibitor (antagomir) markedly reduced lesion volume, brain water contents and neuron death in TBI mice induced by the controlled cortical impact (CCI). In addition, cognitive dysfunction in TBI mice was markedly improved after miR-193a antagomir injection. Of note, CCI-induced activation of microglia was repressed by miR-193a inhibition, along with significantly reduced expression of neuroinflammatory markers, which were associated with the blockage of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. The anti-neuroinflammation effects of miR-193a suppression were verified in lipopolysaccharide (LPS)-incubated microglial cells transfected with miR-193a inhibitor. In contrast, LPS-induced activation of microglial cells and the expression of pro-inflammatory factors was markedly further accelerated by the transfection of miR-193a mimic. Taken together, TBI resulted in a robust neuroinflammatory response that was closely associated with the up-regulated miR-193a expression mainly in microglia/macrophages; however, miR-193a suppression significantly alleviated post-traumatic neuroinflammation and cognitive dysfunction. Therefore, miR-193a might be a promising therapeutic target for the treatment of TBI-associated neuroinflammation.

10.
Calcif Tissue Int ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897529

RESUMO

Ossification of the ligamentum flavum (OLF) is characterized by a process of ectopic bone formation in the ligamentum flavum. The definitive pathophysiology of OLF still remains unclear, but the epigenetic m6A modification plays an important role in OLF. In addition, no studies have reported the function of ALKBH5 in OLF development. In this study, we investigated the function of the m6A demethylation enzyme ALKBH5 in OLF. To evaluate the function of ALKBH5, OLF tissues and normal ligamentum flavum tissues were collected. In vitro methods, including HE, IHC and western blotting assays, were used to evaluate the association of ALKBH5 with OLF. In addition, we verified the effects of ALKBH5 on osteogenesis using alizarin red and ALP staining. MeRIP q-PCR was performed to investigate the methylation level of BMP2. Moreover, the mechanism of ALKBH5-mediated regulation of the ossification of the ligamentum flavum cells through the AKT signaling pathway was also verified. The present study showed that the expression of ALKBH5 increased in OLF tissues. The overexpression of ALKBH5 increased the expression of osteogenic genes and promoted the ossification of ligamentum flavum cells. Furthermore, BMP2 was significantly enriched in the ligamentum flavum cells of the anti-m6A group compared with those of the IgG group. The overexpression of ALKBH5 led to the activation of p-AKT, and BMP2 was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. ALKBH5 was shown to be an important demethylation enzyme in OLF development.

11.
Magn Reson Med ; 83(5): 1659-1672, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31658397

RESUMO

PURPOSE: To propose a parameter optimization framework on wave gradients of Wave-CAIPI imaging for decreasing g-factor penalty and reducing reconstruction artifacts. THEORY AND METHODS: The influences of parameters on g-factor are theoretically analyzed. The average g-factor is chosen as a metric for parameter optimization, and then a fast calculation method is proposed to approximately and ultra-fast calculate the average g-factor. Based on this, a set of points in the function of the average g-factor with respect to the wave gradient parameters is calculated, and the optimal wave gradient parameters are found according to these points. RESULTS: In vivo human brain experiments were performed on 3T MR scanners for the comparison experiments. The results show that the proposed parameter optimization framework is able to efficiently obtain optimal wave gradient parameters, which can achieve decreased g-factor penalty and less artifacts of reconstructions than the empirical parameters. CONCLUSION: The proposed parameter optimization framework is computationally efficient and can optimize the wave gradient parameters of Wave-CAIPI imaging for better image quality than before.

12.
Chin Med J (Engl) ; 133(2): 127-133, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31880744

RESUMO

BACKGROUND: The role of local treatment in oligometastatic prostate cancer (PCa) is gaining interest with the oligometastases hypothesis proposed and the improvement of various surgical methods and techniques. This study aimed to compare the short-term therapeutic outcomes of robotic-assisted laparoscopic radical prostatectomy (RALP) for oligometastatic prostate cancer (OPC) vs. localized PCa using propensity score matching. METHODS: Totally 508 consecutive patients underwent RALP as a first-line treatment. The patients were divided into two groups according to oligometastatic state: the OPC group (n = 41) or the localized PCa group (n = 467). Oligometastatic disease was defined as the presence of two or fewer suspicious lesions. The association between the oligometastatic state and therapeutic outcomes of RALP was evaluated, including biochemical recurrence (BCR) and overall survival (OS). A Cox proportional hazards model was used to assess the possible risk factors for BCR. RESULTS: Totally 41 pairs of patients were matched. The median operative time, the median blood loss, the overall positive surgical margin rate, the median post-operative hospital stays, and the post-operative urinary continence recovery rate between the two groups showed no statistical significance. The 4-year BCR survival rates of the OPC group and localized PCa group were 56.7% and 60.8%, respectively, without a significant difference (P = 0.804). The 5-year OS rates were 96.3% and 100%, respectively (P = 0.326). Additionally, the results of Cox regression showed that oligometastatic state was not an independent risk factor for BCR (P = 0.682). CONCLUSIONS: Our findings supported the safety and effectiveness of RALP in OPC. Additionally, oligometastatic state and sites did not have an adverse effect on BCR independently.

13.
Nature ; 577(7788): 79-84, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31853069

RESUMO

Water lilies belong to the angiosperm order Nymphaeales. Amborellales, Nymphaeales and Austrobaileyales together form the so-called ANA-grade of angiosperms, which are extant representatives of lineages that diverged the earliest from the lineage leading to the extant mesangiosperms1-3. Here we report the 409-megabase genome sequence of the blue-petal water lily (Nymphaea colorata). Our phylogenomic analyses support Amborellales and Nymphaeales as successive sister lineages to all other extant angiosperms. The N. colorata genome and 19 other water lily transcriptomes reveal a Nymphaealean whole-genome duplication event, which is shared by Nymphaeaceae and possibly Cabombaceae. Among the genes retained from this whole-genome duplication are homologues of genes that regulate flowering transition and flower development. The broad expression of homologues of floral ABCE genes in N. colorata might support a similarly broadly active ancestral ABCE model of floral organ determination in early angiosperms. Water lilies have evolved attractive floral scents and colours, which are features shared with mesangiosperms, and we identified their putative biosynthetic genes in N. colorata. The chemical compounds and biosynthetic genes behind floral scents suggest that they have evolved in parallel to those in mesangiosperms. Because of its unique phylogenetic position, the N. colorata genome sheds light on the early evolution of angiosperms.

14.
J Neurosci Methods ; 329: 108466, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31628961

RESUMO

BACKGROUND: Stroke is the third most common cause of disability and the second most common cause of death worldwide. Ischemia, one of the two broad categories of stroke, is characterized by a lack of sufficient amounts of blood in order to supply an adequate amount of oxygen and nutrients. It is important to assess the part of the brain that becomes ischemic and necrotic during neurosurgery or experiments in real time. However, there is currently no effective means to achieve this goal. NEW METHOD: We proposed a method based on hyperspectral imaging (HSI) for the real-time detection of a varied range of ischemic brain tissues in vivo or ex vivo and assessed the practical utility of a model of ischemic stroke in rats. RESULTS: The results showed that hyperspectral images processed with a ratio of spectral reflectance at 545 and 560 nm (R545/R560) could identify early brain ischemia and accurately show regions of ischemia. COMPARISON WITH EXISTING METHODS: We verified the area imaged by HSI using hematoxylin and eosin (HE) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining methods. This technique could precisely image the ischemic part of the brain in vivo and ex vivo. CONCLUSIONS: These results demonstrate the practical utility of HSI for the real-time detection of cerebral ischemia in rats. By providing rapid assessment of brain tissue perfusion, HSI may help doctors recognize ischemic regions quickly and precisely during surgery as well as have great utility in the experimental process.

15.
Ann Work Expo Health ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785204

RESUMO

OBJECTIVES: National Institute for Occupational Safety and Health-approved P100 filtering facepiece respirators (FFRs) have a higher filter efficiency compared to the N95 filters. However, the former typically produce higher flow resistance (Rf). Consequently, when faceseal leakage is present, the proportion of leakage airflow for P100 FFRs may exceed that of N95s, resulting in a higher total inward leakage (TIL) of the P100. METHODS: In this manikin-based study, the performance of two pairs of N95 and P100 FFRs (N95-A versus P100-A; N95-B versus P100-B) were compared under five sealing conditions (fully sealed and partially sealed with one, two, or three leaks of 0.8-mm, and one 2-mm leak). Sodium chloride particles (CMD ~45 nm) were used as the challenge aerosol. Respirators were tested under three constant flows (15, 50, and 85 L/min) and three cyclic flows (mean inspiratory flow = 15, 50, and 85 L/min). Both filter penetration (Pfilter) and TIL were determined. The Rf under constant flows was recorded. Based on Pfilter, TIL, and Rf, the quality factor (qf) was calculated to compare the overall performance of N95 and P100 FFRs. RESULTS: For a fully sealed condition, the Pfilter was much lower for the P100 FFRs than for the N95 FFRs. When small leaks were inserted (0.8-mm and 2 × 0.8-mm), the TIL was higher for the P100 FFRs than for the N95 FFRs under the lowest tested flow (15 L/min), while for greater leaks (3 × 0.8-mm and 2-mm), the TIL of the P100 FFRs was always higher regardless of the flow. The Rf of P100 FFRs was measured twice as high as the N95. The qf values were also found higher for the N95 FFRs than for the P100 FFRs regardless of leak size and breathing flow. CONCLUSIONS: With the presence of artificial leakage, a P100 FFR with high-flow-resistance may not be as protective as a low-flow-resistance N95 FFR. This finding suggests that future efforts should be directed to reducing the breathing resistance when designing P100 FFRs.

16.
Transl Androl Urol ; 8(5): 507-518, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807427

RESUMO

Background: Metabolic syndrome (MetS) has been found to be prevalent in cancer and have implications in cancer outcomes. In this study, we attempted to evaluate the prognostic value of MetS in localized clear cell renal cell carcinoma (ccRCC) patients. Methods: We retrospectively collected clinicopathological data and pre-treatment laboratory test results of 480 patients with localized (T1-2N0M0) ccRCC undergoing radical or partial nephrectomy in Peking University First Hospital. MetS was diagnosed by criteria of the 2004 Chinese Medical Association Diabetes Society. Univariate and multivariate analyses were conducted to analyze the association between clinicopathological characteristics, MetS, and disease outcomes. Results: In our cohort, 136 patients (28.3%) were diagnosed with MetS. Among them, 113 (83.1%) were men, suggesting that men were more likely to have MetS. This syndrome was also associated with increased pre-treatment creatinine levels. Median follow-up time was 70 months (range, 1-118 months) and 5-year overall survival (OS) rate was 92%. MetS was an independent favorable factor of cancer-specific survival (CSS) (P=0.017), and similar results were observed in Fuhrman nuclear grade 1-2 ccRCC patients by further analysis. Neither of the four components of the MetS (hypertension, diabetes mellitus, overweight/obesity and dyslipidemia) was an independent predictor of CSS. Patients who met more than 3 of the 4 criteria for MetS had higher CSS than those who met fewer than 2 criteria. Conclusions: MetS is an independent prognostic factor for better CSS in localized ccRCC patients.

17.
Med Phys ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31872450

RESUMO

PURPOSE: To develop a novel three-dimensional (3D) hybrid-encoding framework using compressed sensing (CS) and Toeplitz encoding with variable phase-scrambled radio-frequency (RF) excitation, which has the following advantages: low power deposition of RF pulses, reduction of the signal dynamic range, no additional hardware requirement, and signal-to-noise ratio (SNR) improvement. METHODS: In light of the actual imaging framework of magnetic resonance imaging (MRI) scanners, we applied specially tailored RF pulses with phase-scrambled RF excitation to implement a 3D hybrid Fourier-Toeplitz encoding method based on 3D gradient-recalled echo pulse (GRASS) sequence. This method exploits Toeplitz encoding along the phase encoding direction, while keeping Fourier encoding along the readout and slice encoding directions. Phantom experiments were conducted to optimize the amplitude of specially tailored RF pulses in the 3D GRASS sequence. In vivo experiments were conducted to validate the feasibility of the proposed method, and simulations were conducted to compare the 3D hybrid-encoding method with Fourier encoding and other non-Fourier encoding methods. RESULTS: An optimized low RF amplitude was obtained in the phantom experiments. Using the optimized specially tailored RF pulses, both the watermelon and knee experiments demonstrated that the proposed method was able to preserve more image details than the conventional 3D Fourier-encoded methods at acceleration factors of 3.1 and 2.0. Additionally, SNR was improved because of no additional gradients and 3D volume encoding, when compared with single-slice scanning without 3D encoding. Simulation results demonstrated that the proposed scheme was superior to the conventional Fourier encoding method, and obtained comparative performance with other non-Fourier encoding methods in preserving details. CONCLUSIONS: We developed a practical hybrid-encoding method for 3D MRI with specially tailored RF pulses of phase-scrambled RF excitation. The proposed method improves image SNR and detail preservation compared with the conventional Fourier encoding methods. Furthermore, our proposed method exhibits superior performance in terms of detail preservation, compared with the conventional Fourier encoding method.

18.
Trials ; 20(1): 735, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842969

RESUMO

BACKGROUND: The incidence, mortality, and prevalence of chronic obstructive pulmonary disease (COPD) are high in China. Acute exacerbations of COPD (AECOPD) are important events in the management of COPD because they negatively impact health status, rates of hospitalization and readmission, and disease progression. AECOPD have been effectively treated with Chinese medicine for a long time. The aim of this proposed trial is to assess the therapeutic effect of Chinese medicine (CM) on AECOPD. METHODS/DESIGN: This proposed study is a multicenter, double-blind, parallel-group randomized controlled trial (RCT). We will randomly assign 378 participants with AECOPD into two groups in a 1:1 ratio. On the basis of health education and conventional treatment, the intervention group will be treated with CM, and the control group is given CM placebo according to CM syndrome. Patients are randomized to either receive CM or placebo, 10 g/packet, twice daily. The double-blind treatment lasts for 2 weeks and is followed up for 4 weeks. The main outcome is the COPD Assessment Test; secondary outcomes are treatment failure rate, treatment success rate, length of hospital stay, AECOPD readmission rate, intubation rate, mortality, dyspnea, the 36-item Short Form Health Survey, and the COPD patient-reported outcome scale. We will document these outcomes faithfully at the beginning of the study, 2 weeks after treatment, and at the 4 weeks follow-up. DISCUSSION: This high-quality RCT with strict methodology and few design deficits will help to prove the effectiveness of CM for AECOPD. We hope this trial will provide useful evidence for developing a therapeutic schedule with CM for patients with AECOPD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03428412. Registered on 4 February 2018.

19.
Ann Surg Oncol ; 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848822

RESUMO

PURPOSE: To develop and internally validate nomograms to help choose the optimal biopsy strategy among no biopsy, targeted biopsy (TB) only, or TB plus systematic biopsy (SB). PATIENTS AND METHODS: This retrospective study included a total of 385 patients who underwent magnetic resonance imaging (MRI)-guided TB and/or SB at our institute after undergoing multiparametric MRI (mpMRI) between 2015 and 2018. We developed models to predict clinically significant prostate cancer (csPCa) based on suspicious lesions from a TB result and based on the whole prostate gland from the results of TB plus SB or SB only. Nomograms were generated using logistic regression and evaluated using receiver-operating characteristic (ROC) curve analysis, calibration curves and decision analysis. The results were validated using ROC curve and calibration on 177 patients from 2018 to 2019 at the same institute. RESULTS: In the multivariate analyses, prostate-specific antigen level, prostate volume, and the Prostate Imaging Reporting and Data System score were predictors of csPCa in both nomograms. Age was also included in the model for suspicious lesions, while obesity was included in the model for the whole gland. The area under the curve (AUC) in the ROC analyses of the prediction models was 0.755 for suspicious lesions and 0.887 for the whole gland. Both models performed well in the calibration and decision analyses. In the validation cohort, the ROC curve described the AUCs of 0.723 and 0.917 for the nomogram of suspicious lesions and nomogram of the whole gland, respectively. Also, the calibration curve detected low error rates for both models. CONCLUSION: Nomograms with excellent discriminative ability were developed and validated. These nomograms can be used to select the optimal biopsy strategy for individual patients in the future.

20.
Clin Lab ; 65(12)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31850704

RESUMO

BACKGROUND: Chemotherapy constitutes one of the most important adjuvant treatments for bladder cancer. However, many patients usually develop chemoresistance during chemotherapy. At present, lncRNA has been confirmed not only to be involved in tumorigenesis and progression, but also in tumor chemoresistance. However, the relationship between lncRNAs and chemoresistance of bladder cancer have been rarely reported. METHODS: The novel lncRNA-KMU15 was screened by lncRNAs microarray and determination of IC50 in bladder cancer. The expression of KMU15 was evaluated by qRT-PCR. The correlation between KMU15 and clinicopathological parameters was analyzed from clinical cases. The effects of KMU15 on the biological behavior and chemoresistance were investigated by [3H]-TdR incorporation assay and other experiments. The effects of KMU15 on the growth of xenograft tumors and the survival of nude mice under cisplatin were examined in a xenograft mouse model. RESULTS: We confirmed that KMU15 was expressed higher in bladder cancer tissues than paired control tissues. Moreover, the expression of KMU15 was significantly positively correlated with the grade, stage, metastasis, and recurrence of bladder cancer and was significantly negatively correlated with the prognosis. In addition, KMU15 knockdown could significantly inhibit bladder cell proliferation, adhesion, migration, and chemoresistance and promoted apoptosis. Knockdown of KMU15 inhibited the growth of xenografts in nude mice and significantly prolonged the survival of tumor-bearing mice under cisplatin. CONCLUSIONS: The novel lncRNA KMU15, which is highly expressed in bladder cancer tissues, could promote the proliferation and progression and was closely related to the malignant degree of bladder cancer. It could also significantly enhance the chemoresistance of bladder cancer cells. Therefore, it was expected to be a new therapy target for bladder cancer and a potential prognosis biomarker for chemotherapy.

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