We developed a diffusion layer with a refractive index-matching layer added to a transparent nanoscale polymer-based structure to obtain its effective scattering effects. The diffusion layer had higher haze when the refractive index-matching layer to a higher refractive index was used. This diffusion layer was applied to conventional organic light-emitting diodes (OLEDs) and micro-cavity OLEDs (MC-OLEDs) to evaluate the characteristics. When a diffusion layer was applied to conventional OLEDs, the external quantum efficiency (EQE) was 31.1% higher than that of the device without a diffusion layer due to the reduction of the substrate mode, and the viewing angle characteristic was also improved. Then, when the diffusion layer was applied to the MC-OLEDs, all devices showed similar EQE values regardless of the presence or absence of the diffusion layer, and the viewing-angle-dependent characteristics were greatly improved by the diffusion layer. Furthermore, when the diffusion layer was used with polarizer film, the black color implementation was not affected by the polarizer film, proving that it is applicable to actual OLED display products.

A new mechanism is revealed by which a polyphenol, rosmarinic acid (RA), suppresses amyloid β (Aβ) accumulation in mice. Here we examined the brains of mice (Alzheimer's disease model) using DNA microarray analysis and revealed that the dopamine (DA)-signaling pathway was enhanced in the group fed RA versus controls. In the cerebral cortex, the levels of monoamines, such as norepinephrine, 3,4-dihydroxyphenylacetic acid, DA, and levodopa, increased after RA feeding. The expression of DA-degrading enzymes, such as monoamine oxidase B (Maob), was significantly downregulated in the substantia nigra and ventral tegmental area, both DA synthesis regions. Following in vitro studies showing that monoamines inhibited Aβ aggregation, this in vivo study, in which RA intake increased concentration of monoamine by reducing Maob gene expression, builds on that knowledge by demonstrating that monoamines suppress Aβ aggregation. In conclusion, RA-initiated monoamine increase in the brain may beneficially act against AD.

The prevalence of a macrophage phenotype in atherosclerotic plaque may drive its progression and/or instability. Macrophages from coronary plaques are not available, and monocyte-derived macrophages (MDMs) are usually considered as a surrogate. We compared the MDM profile obtained from coronary artery disease (CAD) patients and healthy subjects, and we evaluated the association between CAD MDM profile and in vivo coronary plaque characteristics assessed by optical coherence tomography (OCT). At morphological analysis, MDMs of CAD patients had a higher prevalence of round than spindle cells, whereas in healthy subjects the prevalence of the two morphotypes was similar. Compared to healthy subjects, MDMs of CAD patients had reduced efferocytosis, lower transglutaminase-2, CD206 and CD163 receptor levels, and higher tissue factor (TF) levels. At OCT, patients with a higher prevalence of round MDMs showed more frequently a lipid-rich plaque, a thin-cap fibroatheroma, a greater intra-plaque macrophage accumulation, and a ruptured plaque. The MDM efferocytosis correlated with minimal lumen area, and TF levels in MDMs correlated with the presence of ruptured plaque. MDMs obtained from CAD patients are characterized by a morpho-phenotypic heterogeneity with a prevalence of round cells, showing pro-inflammatory and pro-thrombotic properties. The MDM profile allows identifying CAD patients at high risk.

Neuroinflammation is one of the critical events in neurodegenerative diseases, whereas microglia play an important role in the pathogenesis of neuroinflammation. In this study, we investigated the effects of a natural sesquiterpene lactone, 6-O-angeloylplenolin (6-OAP), isolated from the traditional Chinese medicine Centipeda minima (L.) A.Br., on neuroinflammation and the underlying mechanisms. We showed that treatment with lipopolysaccharide (LPS) caused activation of BV2 and primary microglial cells and development of neuroinflammation in vitro, evidenced by increased production of inflammatory cytokines TNF-α and IL-1β, the phosphorylation and nuclear translocation of NF-κB, and the transcriptional upregulation of COX-2 and iNOS, leading to increased production of proinflammatory factors NO and PGE2. Moreover, LPS treatment induced oxidative stress through increasing the expression levels of NOX2 and NOX4. Pretreatment with 6-OAP (0.5-4 μM) dose-dependently attenuated LPS-induced NF-κB activation and oxidative stress, thus suppressed neuroinflammation in the cells. In a mouse model of LPS-induced neuroinflammation, 6-OAP (5-20 mg·kg-1·d-1, ip, for 7 days before LPS injection) dose-dependently inhibited the production of inflammatory cytokines, the activation of the NF-κB signaling pathway, and the expression of inflammatory enzymes in brain tissues. 6-OAP pretreatment significantly ameliorated the activation of microglia and astrocytes in the brains. 6-OAP at a high dose caused a much stronger antineuroinflammatory effect than dexamethansone (DEX). Furthermore, we demonstrated that 6-OAP pretreatment could inhibit LPS-induced neurite and synaptic loss in vitro and in vivo. In conclusion, our results demonstrate that 6-OAP exerts antineuroinflammatory effects and can be considered a novel drug candidate for the treatment of neuroinflammatory diseases.

Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited disease caused by three missense mutations of mitochondrial (mt) DNA, ie, m 3460 G>A, m 11778 G>A, or m 14484 T>C in the greater portion of LHON. m 11778 G>A mutation is especially observed in >90% of the cases in Japanese families. Although spontaneous remission of visual function infrequently occurs, effective treatment for LHON remains unestablished. Transcorneal electrical stimulation has been shown to be efficacious in individuals with optic neuropathy. However, due to potential risk of corneal damage, repeated treatments are not permissible. In this exploratory study, we will be conducting skin electrical stimulation (SES) as an intervention for patients with LHON having 11778 missense mutation and investigate effectiveness and safety of SES. Methods: This is a single-arm, prospective, open-label exploratory trial focused on patients with LHON having 11778 missense mutation. Eleven patients will be enrolled and receive six consecutive SES once every 2 weeks up to 10 weeks. The safety of the SES will be monitored with specular microscopy, slit-lamp biomicroscopy, fundus examinations, and the observation of facial skin. The primary outcome measure will be the averaged l ogarithm of minimum angle resolution (logMAR) converted visual acuity 1 week after the last SES. Secondary outcome measures include changes, in logMAR at 4 and 8 weeks after the last SES, such as visual field indices measured using Humphrey visual field and microperimetry-3, the thickness of peripapillary retinal fiber and macular ganglion cell complex, multifocal visual evoked potentials, critical flicker frequency, and color vision. Discussion: The results of this proposed proof-of-concept feasibility trial will help plan and execute a larger definitive trial to test SES as an effective strategy for LHON and related optic neuropathies and help establish a beneficial treatment for LHON.

Background: To evaluate the effects of resveratrol to monocyte chemoattractant protein-1 (MCP-1) and the role of p38 mitogen-activated protein kinase (MAPK) in this process in vitro. Materials and methods: Animal acute pulmonary thromboembolism (PTE) model: rat model was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter. One hundred and thirty-two rats were randomly and equally divided into ten groups: rats-control (untreated), rats-1% DMSO, rats-TNF-α, rats-TNF-α + resveratrol, rats-TNF-α +C1142, rats-TNF-α+SB203580, rats-TNF-α+resveratrol + SB203580, rats-resveratrol only, rats-C1142 only, and rats-SB203580 only. Rat pulmonary artery endothelial cells (RPAs) tests: RPAs were isolated from above animal and designated as: RPAs-control, RPAs-1% DMSO control, RPAs-TNF-α, RPAs-TNF-α + resveratrol, RPAs-TNF-α + C1142, RPAs-TNF-α + SB203580, RPAs-TNF-α + resveratrol + SB203580, RPAs-resveratrol only, RPAs-C1142 only, and RPAs-SB203580 only. Each group was further divided into 1, 4, and 8 hrs time point for evaluation (n=6 rats per time point) except RPAs-TNF-α + SB203580, RPAs-TNF-α + resveratrol + SB203580, RPAs-C1142 and RPAs-SB203580 only, which were evaluated at 8 hrs time point. At each time point, mRNA and protein expressions of RPAs of MCP-1 were measured. The phosphorylation of p38 MAPK (p-pMAPK) of RPAs was also detected. Results: We found that the RPAs-TNF-α elicited significant increases in MCP-1 expression and phosphorylation of p38 mitogen-activated protein kinase (p-p38 MAPK). Furthermore, the MCP-1 expressions of RPAs-Resveratrol, RPAs-C1142, and RPAs-SB203580 were significantly down-regulated, which was associated with robustly suppressed TNF-α-induced p-p38MAPK expression. Conclusion: Our findings suggested that MCP-1 was involved in the formation of TNF-α-induced inflammatory response, and resveratrol could down-regulate the expression of MCP-1 via TNF-α- inhibition, which might contribute to the decline of acute PTE-induced PH in vivo.

Background: Improving glycemic control requires that patients actively participate in decisions about how to best live with the disease and adapt to the realities of self-care. Limited health literacy (HL) is related to poorer health outcomes and may make it difficult for patients to participate in shared decision-making (SDM). As such, understanding the relationship between HL and SDM and its impact on diabetes control is an urgent issue. Methods: A cross-sectional survey was conducted among outpatients with type 2 diabetes in a regional teaching hospital. Purposive sampling was used to recruit eligible 372 patients via self-administered questionnaires. HbA1C values were obtained from each patient's laboratory assay. Results: Among the 372 participants, 50.4% of patients preferred physician decision-making, 39.3% preferred SDM, and 10.3% preferred patient decision-making. The physician explaining the illness in colloquial language, having adequate time for discussion, and encouragement from the healthcare provider were the major factors influencing patients' involvement in SDM. Interactive HL and critical HL had positive correlations with patients' perceived involvement in SDM. Educational attainment and HL were positively related. The HbA1C values for patient decision-making and physician decision-making were approximately 1.4 times and 1.24 times higher than those of SDM, respectively. Conclusion: SDM led to better glycemic control. HL increased patients' perceived involvement in SDM. Therefore, it is necessary to improve levels of HL based on the educational attainment of patients. Physicians explaining illness in colloquial language is the key factor in promoting patients' perceived involvement in SDM.

To bridge the efficacy and compare the safety of the 24-week teriparatide treatment in a Chinese osteoporosis study (NCT00414973) to a large international trial (FPT, NCT00670501) to determine whether long-term results from the international study were applicable to Chinese patients.

Background: Pulmonary hypertension (PH) is one of the most common complications developed during the course of chronic obstructive pulmonary disease (COPD). Platelet activation plays an important role in its pathophysiology, and mean platelet volume (MPV) is considered a respectable index of platelet activation. The aim of this work is to assess the ability of MPV in predicting PH secondary to COPD as well as its severity. Methods: A cross-sectional study was conducted on 228 stable COPD patients. CBC, echocardiography, and pulmonary function tests were performed. Results: The prevalence of PH in stable COPD patients was high (63%), and the majority of patients had a mild degree (33%). There was no significant association between PH presence with different COPD grade, but, in very severe COPD, severe PH was significantly presented. MPV in COPD patients with PH was significantly higher than those without (9.02±1.14 vs 7.11±0.98, P<0.001). Moreover, a significant statistical rising of MPV with increased severity of PH. Multivariate regression analysis of predictors of PH demonstrated that; MPV is a real predictor of PH in such patients. The likelihood probability of PH increased up to 7-times with increasing one unit of MPV; (OR=6.7). A cut-off value of MPV >7.25 had 96% sensitivity and 76% specificity in predicting PH. Conclusion: MPV was higher in COPD patients with PH and positively correlated with PH severity. If the data are to be confirmed, MPV may be taken into consideration in decision-making and management of COPD patients.

Background: In vivo fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window using organic fluorophores has great advantages, but generally suffers from a relatively low fluorescence quantum yield (mostly less than 2%). In this study, organic nanoparticles (L1013 NPs) with a high fluorescence quantum yield (9.9%) were systhesized for in vivo imaging. Methods: A molecule (BTPPA) with donor-acceptor-donor structure and aggregation-induced emission enabling moieties was prepared. BTPPA molecules were then encapsulated into nanoparticles (L1013 NPs) using a nanoprecipitation method. The L1013 NPs were intravenously injected into the mice (including normal, stroke and tumor models) for vascular and tumor imaging. Results: L1013 NPs excited at 808 nm exhibit NIR-II emission with a peak at 1013 nm and an emission tail extending to 1400 nm. They have a quantum yield of 9.9% and also show excellent photo/colloidal stabilities and negligible in vitro and in vivo toxicity. We use L1013 NPs for noninvasive real-time visualization of mouse hindlimb and cerebral vessels (including stroke pathology) under a very low power density (4.6-40 mW cm‒2) and short exposure time (40-100 ms). Moreover, L1013 NPs are able to localize tumor pathology, with a tumor-to-normal tissue ratio of 11.7±1.3, which is unusually high for NIR-II fluorescent imaging through passive targeting strategy. Conclusion: L1013 NPs demonstrate the potential for a range of clinical applications, especially for tumor surgery.

Background and purpose: Traumatic brain injury (TBI) is a major disease without effective treatment. Recently, Tat-NR2B9c peptide emerged as a promising neuroprotective agent, but limited in clinical translation by it low brain penetrability. We synthesized Tat-NR2B9c loaded self-assembled activatable protein nanoparticles, termed TN-APNPs, and demonstrated that TN-APNPs enhanced the delivery of Tat-NR2B9c to the brain lesion in stroke. Herein we developed a novel approach to further engineering TN-APNPs for targeted delivery of Tat-NR2B9c to the injured brain with enhanced efficiency through conjugation of CAQK or CCAQK, a short peptide. Methods: Short peptide-conjugated TN-APNPs were synthesized by conjugated with CAQK or CCAQK via a click condensation reaction with CBT, then analyzed by dynamic light scattering, transmission electron microscopy and thrombin responsive assay. Characterization of short peptide-conjugated TN-APNPs were investigated by using cell excitotoxicity assay and transwell blood-brain-barrier model in vitro, and pharmacokinetics, IVIS imaging system and confocal analysis in TBI-bearing mice. Evaluation of therapeutic effects were analyzed by H&E staining, Elevated Plus Maze analysis and Rotarod test. Results: CAQK-conjugated TN-APNPs (C-TN-APNPs) and CCAQK-conjugated TN-APNPs (CC-TN-APNPs) were spherical in morphology and 30 nm in diameter. In vitro studies revealed that TN-APNPs, C-TN-APNPs and CC-TN-APNPs were responsive to thrombin cleavage, reduced the cytotoxicity of Tat-NR2B9c, and increased BBB permeability of Tat-NR2B9c. CC-TN-APNPs demonstrated the better circulation time, better targeting ability and penetrating efficiency to the injured brain, and better therapeutic benefits in vivo studies. Conclusion: This study demonstrated CC-TN-APNPs as a promising therapeutic for clinical management of TBI.

Background: Accumulating evidence has demonstrated that single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) (referred to as miR-SNPs) participate in the process of carcinogenesis by altering the expression and structure of mature miRNAs. However, the associations between several previously reported miR-SNPs, including miR-196a2 rs11614913, miR-146a rs2910164, miR-34b/c rs4938723, and miR-423 rs6505162 and the susceptibility of esophageal squamous cell carcinoma (ESCC) remain controversial. We, therefore, performed a comprehensive meta-analysis to systemically evaluate the correlation of genetic polymorphisms in these four miRNAs with the risk of ESCC. Methods: Relevant studies were searched in PubMed and other electronic databases up to August 2018, supplemented by a manual search of references from retrieved articles. The pooled ORs with 95% CIs were calculated using a random-effects model. Results: A total of 22 studies from 13 published articles were included in the meta-analysis. All studies have a relatively high score of quality assessment. The pooled analysis indicated that individuals with the variant TT genotype of rs11614913 in miR-196a2 gene have a significantly decreased risk of ESCC compared with CC genotype (OR =0.83, 95% CI: 0.73-0.95). The decreased risk of ESCC was also shown in the recessive model (TT vs CT/CC: OR=0.86, 95%CI: 0.77-0.96) and allele model (T vs C: OR=0.93, 95%CI: 0.87-0.99). The significantly reduced risk of ESCC was also observed in the polymorphisms of the miR-34b/c rs4938723 locus. The similar tendency was presented in the subgroup of Chinese Han population when stratified by ethnicity. However, no significant associations were observed in the miR-146a rs2910164 and miR-423 rs6505162 with the susceptibility of ESCC in any genetic model. Conclusion: Our results suggested that the polymorphisms of miR-196a and miR-34b/c genes were related to the risk of ESCC, especially among Chinese. The findings of this study, however, need to be confirmed in further researches.

Background: Renal cancer is one of the most common malignancies. However, the mechanisms underlying its development are still ambiguous. B7-H3 has been described as an important tumor antigen in various human tumors. An abnormal high expression of B7-H3 molecules is often observed in tumor cells and tumor stromal cells in the tumor microenvironment. On the basis of the above findings, we hypothesized that cancer-associated fibroblasts (CAFs) clustered in the renal cell microenvironment can survive for a long time with the anti-apoptotic effect of B7-H3, and then secrete cytokines to enhance the malignant behavior of renal cancer cells. Methods: The expression of B7-H3 protein in CAFs was detected in renal cancer tissues. Then, the CAFs cells were stably transfected with shRNA and their expression was silenced to determine the role of B7-H3 in CAFs. Western blot was used to detect the expression of apoptosis-related proteins, hepatocyte growth factor (HGF) protein and stromal cell-derived factor-1 (CXCL12) protein. CAF-NC cells and CAFs-shRNA cells were co-cultured with A498 cells to assess the biological function changes of A498. Results: A group of CAFs were found with B7-H3 expression in renal cancer. B7-H3 can stimulate CAFs to secrete HGF and Cxcl-12, and has strong anti-apoptotic effect on CAFs. We also found that CAFs-NC promotes the proliferation, invasion and migration of A498 cells in vitro and promotes the tumor formation of A498 in vivo. Conclusion: B7-H3+ CAFs promote the invasion and metastasis in renal cancer.

Purpose: Glioma is a refractory disease associated with immune cell infiltration, and the effectiveness of checkpoint blockade remains suboptimal. As an adhesion and costimulatory molecule, CD48 plays a significant role in immunomodulation. As such, studying CD48 may provide additional understanding of the immune and inflammation response of glioma. Methods: Using R language and GraphPad Prism 7, RNA sequencing data of 946 patients from Chinese Glioma Genome Atlas and The Cancer Genome Atlas cohorts were analyzed. Results: CD48 was highly expressed in the malignant progression of glioma. As an independent risk factor, high-CD48 patients were associated with poor prognosis. CD48 influenced glioma purity and the local immune cell subpopulation. CD48 was closely related to immune function in glioma. Patients with an enhanced immune phenotype, high CD48, were associated with immune suppressive molecules and checkpoints. In addition, CD48 correlated with the immune and inflammatory response. A checkpoint risk score including CD48, SLAMF8 and PD-L1 was used to assess the role of checkpoints. Risk score was particularly high in a malignant subtype of glioma and was an independent predictive indicator of unfavorable outcome. Additionally, age, IDH subtype and MGMT promoter status influenced the predictive significance of checkpoint risk score. Conclusion: CD48 exhibits a crucial role in reduced survival and immunomodulation in glioma. In addition, we found that checkpoints play a greater role in patients older than 40 years old with IDH wild-type and MGMT methylated status. These findings suggest that combining CD48 blockade with PD-L1 may be a promising approach to glioma immunotherapy for specific subpopulations of patients.

Aim: The purpose of this study is to evaluate the role of MET T1010I and MET rs40239 as potential risk factor and/or prognostic markers in patients with triple-negative breast cancer (TNBC). Methods: 114 samples of DNA from paraffin-embedded breast normal tissues of patients with TNBC and 124 samples of healthy controls were collected and analyzed for MET T1010I and MET rs40239 polymorphisms. Results: MET T1010I CT genotype was associated with increased risk of TNBC in both univariate and multivariate analysis. The status of rs40239 was not associated with a higher risk for TNBC at either the univariate or the multivariate analysis. None of the examined polymorphisms was associated with overall survival at the univariate or multivariate Cox regression analysis (adjusted HR=1.35, 95% CI: 0.31-5.97 for MET T1010I CT/TT vs CC; adjusted HR=1.78, 95% CI: 0.73-4.35 for rs40239 AG/GG vs AA). Conclusion: Our case-control study suggests that MET T1010I seems to be a risk factor for TNBC in the Caucasian Greek population, in contrast with MET rs40239, where no correlation was found.

Background: In cancers, tumor-associated macrophages (TAMs) play an important role in the progression, evasion of immunity and sensitivity to therapy. Unfortunately, radiation and hypoxia could induce the M2 macrophages infiltration and polarization. Materials and methods: In this study, we investigated the relevance of macrophage recruitment with radiation and hypoxia by transwell. We also evaluated the effect of β-elemene on the infiltration of M2 macrophages and explored its underlying molecular mechanism by a series of in vitro and in vivo experiments. Results: Irradiated or hypoxia lung cancer cells recruit macrophages, and the recruitment is MCP-1 dependent. We also found that radiation and hypoxia-induced MCP-1 secretion follows upregulation of Prx-1, which leads to nuclear accumulation of NF-κB and HIF-1α expression. In addition, β-elemene could effectively suppress this recruitment phenomenon through Prx-1/NF-κB/HIF-1α signaling. Conclusion: Our study showed that radiation and hypoxia significantly promoted the macrophages recruitment. β-elemene could effectively suppress this recruitment phenomenon and MCP-1 expression via inhibiting Prx-1/NF-κB/HIF-1α pathways.

Purpose: Glioma is the most common malignant brain tumor. The molecular mechanisms underlying its malignancy are not fully understood. LAMC1, which encodes extracellular matrix protein laminin γ1, has been implicated in some malignant tumors but has not been systematically evaluated in glioma. The aim of this study was to evaluate the expression of LAMC1 and its clinical significance. Patients and methods: LAMC1 protein expression in 52 fresh-frozen specimens of different pathological grade gliomas and 5 normal brain tissues was detected by Western blotting. Immunohistochemistry was used to detect LAMC1 protein expression in another set of 76 glioma tissues and 8 normal brain tissues. The associations between clinicopathological factors and LAMC1 expression were analyzed. A log-rank test and a multivariate Cox proportional hazards model were used to determine the relationship between LAMC1 expression and patient prognosis. The expression of LAMC1 at the mRNA level was analyzed in the TCGA database. Results: LAMC1 was highly expressed in high-grade glioma tissues, with moderate expression in low-grade gliomas, and weak or no expression in normal brain tissues, as detected by Western blotting and immunohistochemistry. A chi-square test indicated that LAMC1 expression was associated with pathological grade but not with other clinicopathological factors, such as age, sex, and tumor size. LAMC1 expression at the mRNA level was upregulated in high-grade gliomas compared with low-grade gliomas and normal brain tissue in the TCGA database. The Kaplan-Meier plot and log-rank test in our patient series showed that high LAMC1 expression was significantly associated with shorter survival, which was consistent with the TCGA database analysis. A multivariate Cox proportional hazards model revealed that LAMC1 expression, WHO grade, and surgery procedure were significantly correlated with overall survival and progression-free survival. Conclusion: These results demonstrated that LAMC1 may play an important role in glioma progression and may be used in the diagnosis, prognosis, and targeted therapy of glioma patients.

Background: Wilms tumor (WT) is the most common renal tumor in children with diffusely anaplastic or unfavorable histology, indicative of a poor prognosis. Heterogeneous nuclear ribonucleoprotein L (hnRNPL) is an RNA-binding protein (RBP) and a regulator of alternative RNA splicing that plays an important role in the occurrence and development of several cancers. Methods: Next generation sequencing technologies was used to discovery differentially expressed genes between WT and adjacent nontumors. The gene ontology (GO) analysis was performed to uncover the biological functions of differentially expressed genes, and the kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was applied to find out the related signal pathways. Expression levelsof hnRNPL with WT tissues and cells were determined by RT-qPCR.After silencing hnRNPL, the expression of hnRNPL, p53 and Bcl-2 were detected by RT-qPCR and Western blot in WT cell line. The regulatory effects of hnRNPLon proliferative and apoptotic potentials of WT cells were evaluated by MTT and flow cytometry, respectively. RNA-binding protein immuno-precipitation was used to confirm the direct interaction of hnRNPL with p53 mRNA. Mouse xenograft models ofhnRNPL knockdown were established to test the functions in the growth of WT in vivo. Results: High levels of hnRNPL were expressed in WT tissues and cells. Functional analysis revealed that hnRNPL silencing suppressed cell proliferation and promoted cell apoptosis in WT. Molecular mechanism exploration indicated that hnRNPL directly targeted p53. Moreover, knockdown of hnRNPL inhibited the expression of p53 and Bcl2 in WT. Additionally, hnRNPL silencing inhibited the growth of xenograft tumors in vivo. Conclusion: HnRNPL act as p53 mRNA-binding protein, which plays an important role in the proliferation and apoptosis of WT through p53 and Bcl2 pathways and these findings provide new insights into the mechanism of WT pathogenesis.

Objective: Asthma and gastric reflux disease are widespread and often coexisting diseases with complex interactions, leading some to suspect that asthma symptoms of patients with reflux may improve with anti-reflux therapy. The objective of this study was to determine whether pepsin in saliva, indicative of airway reflux, could be detected in patients with asthma of varying severity and test the requirement of citric acid as a pepsin preservative. Methods: Saliva samples were collected in the clinic (with/without citric acid) and upon waking the following morning from 25 asthmatic patients. Enzyme-linked immunosorbent assay was performed for pepsin and interleukin-8 (IL-8), an inflammatory cytokine induced by pepsin in other airway epithelia. Pepsin induction of IL-8 was tested in a lung epithelial cell culture model. Results: Pepsin was detected in saliva from 14/25 patients (56%; mean concentration of pepsin in specimens where observed ±SD =80.3±87.5 ng/mL); significant agreement was found between samples collected in the presence/absence of citric acid. No significant associations were found with pepsin and clinical measures of asthma severity. IL-8 was detected in saliva from 22/25 patients (88%; mean IL-8 in all specimens where observed =3.27±3.91 ng/mL). IL-8 was significantly upregulated in human lung epithelial cells exposed to pepsin at pH7 in vitro (P=0.041). Conclusion: In summary, more than half of the asthma patients in this study were found to have pepsin in their saliva, indicative of airway reflux. These data support the use of salivary pepsin as a noninvasive tool for future investigation of airway reflux in a larger cohort. The data further suggest that collection in citric acid as a sample preservative is not warranted and that pooling of multiple saliva samples collected at various timepoints may improve sensitivity of pepsin detection and reduce costs incurred by multiple sample analysis in future studies.

Purpose: To assess the clinical efficacy and safety of delafloxacin for treating acute bacterial skin and skin structure infections (ABSSSIs) in adult patients. Patients and methods: The Cochrane Library, EBSCO, EMBASE, Ovid Medline, PubMed, and Web of Science databases were searched up to November 2018. Only randomized controlled trials (RCTs) that evaluated delafloxacin and other comparators for the treatment of ABSSSIs were included. The primary outcome was the clinical cure rate and the secondary outcomes were microbiological response and the risk of adverse events. Results: Four RCTs were included. Overall, delafloxacin exhibited a clinical cure rate similar to the rates of the comparator drugs in the treatment of ABSSSI (OR, 1.05; 95% CI, 0.87-1.27, I2 =16%) and methicillin-resistant Staphylococcus aureus (MRSA)-associated ABSSSI (OR, 1.12; 95% CI, 0.71-1.77, I2 =0%). Delafloxacin had a microbiological eradication (documented and presumed) rate similar to the rates of the comparators in the treatment of ABSSSI (OR, 1.21; 95% CI, 0.58-2.50, I2 =0%) and MRSA-associated ABSSSIs (OR, 1.16; 95% CI, 0.37-3.60, I2 =0%). Delafloxacin and the comparators did not differ significantly in the risk of serious adverse events (AEs), treatment-emergent adverse events (TEAEs), and TEAEs related to the study drug. However, the risk of discontinuation of the study drug due to an AE was lower for delafloxacin than for the comparators (OR, 0.33; 95% CI, 0.15-0.74, I2 =0%). Conclusion: The clinical efficacy of delafloxacin is as high as that of the comparator drugs in the treatment of ABSSSI, including MRSA-associated infections; furthermore, this antibiotic is as well-tolerated as the comparators.