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Background The calcification sign assessed by computed tomography appears to be a potential marker for benignities among patients diagnosed with pulmonary nodules (PNs). The following meta-analysis has been purposefully designed to figure-out the diagnostic value of the calcification signature as a way of identifying benignities from PNs. Methods Cochrane Library, Embase and PubMed were considered as a reference to obtain the required data from January 2000 until October 2020. Stata v12.0 was used as a standard tool for statistical assessment. Results Eleven retrospective studies were assessed via this meta-analysis, which included 6136 PNs (1827 benign and 4309 malignant). The pooled diagnostic odd ratios, positive likelihood ratio (PLR), negative likelihood ratio (NLR), sensitivity and specificity were 6.79, 6.06, 0.89, 13% and 98%, respectively. The value obtained for the area under the curve was 0.65, showing moderate overall diagnostic accuracy. A significant heterogeneity was found while calculating the pooled sensitivity (I2 = 85.5%), specificity (I2 = 75.0%), PLR (I2 = 59.0%), NLR (I2 = 79.5%) and DOR (I2 = 100.0%) in the current analysis. Sub-group analyses presented better PLR and specificity values for the study with a sample size ≥ 400. Deeks' funnel plot asymmetry test detected no potential evidence of significant publication bias (p = 0.091). Conclusions Calcification signs have been identified as moderate regulators corresponding to overall diagnostic performance (via marking a distinct differentiation between malignant and benign) for PNs. However, the manifestation of the calcification sign had a good directive property for benign PNs.

Background:Rhodiola rosea L. has long been used as traditional medicines in Europe and Asia to treat a variety of common conditions and diseases including Alzheimer’s disease, cardiovascular disease, cognitive dysfunctions, cancer, and stroke. Previous studies reported that Rhodiola rosea L. and its components (RRC) improve ischemia stroke in animal models. Here, we conducted a systematic review and meta-analysis for preclinical studies to evaluate the effects of RRC and the probable neuroprotective mechanisms in ischemic stroke.Methods: Studies of RRC on ischemic stroke animal models were searched in seven databases from inception to Oct 2021. The primary measured outcomes included the neural functional deficit score (NFS), infarct volume (IV), brain water content, cell viability, apoptotic cells, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells, B-cell lymphoma-2 (Bcl-2) level and tumor necrosis factor-α (TNF-α) level. The secondary outcome measures were possible mechanisms of RRC for ischemic stroke. All the data were analyzed via RevMan version 5.3.Results: 15 studies involving 345 animals were identified. Methodological quality for each included studies was accessed according to the CAMARADES 10-item checklist. The quality score of studies range from 1 to 7, and the median was 5.53. Pooled preclinical data showed that compared with the controls, RRC could improve NFS (Zea Longa (p < 0.01), modified neurological severity score (mNSS) (p < 0.01), rotarod tests (p < 0.01), IV (p < 0.01), as well as brain edema (p < 0.01). It also can increase cell viability (p < 0.01), Bcl-2 level (p < 0.01) and reduce TNF-α level (p < 0.01), TUNEL-positive cells (p < 0.01), apoptotic cells (p < 0.01).Conclusion: The findings suggested that RRC can improve ischemia stroke. The possible mechanisms of RRC are largely through antioxidant, anti-apoptosis activities, anti-inflammatory, repressing lipid peroxidation, antigliosis, and alleviating the pathological blood brain barrier damage.

Chemoresistance remains a great obstacle in effective lung adenocarcinoma (LUAD) treatment. Previously, we verified the role of microRNA-200b (miR-200b) in the formation of docetaxel (DTX)-resistant LUAD cells. This study aims to investigate the mechanism underlying the low level of miR-200b in DTX-resistant LUAD cells. The real-time reverse transcription (RT2) lncRNA PCR array system was applied to explore lncRNAs that potentially regulated miR-200b in DTX-resistant LUAD cells. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contributed to the low miR-200b level in DTX-resistant LUAD cells. Functional assays were conducted to determine the role of MALAT1 in regulating the growth and metastasis of parental and DTX-resistant LUAD cells. Investigation revealed the mechanism of the competing endogenous RNA (ceRNA) pathway. MALAT1 regulated miR-200b by acting as a ceRNA. MALAT1 modulated the sensitivity of LUAD cells to DTX. E2F transcription factor 3 (E2F3) and zinc-finger E-box binding homeobox 1 (ZEB1) were two targets of miR-200b and mediated the function of MALAT1 in DTX-resistant LUAD cells. Transcription factor AP-2 gamma (TFAP2C) and ZEB1 activated the MALAT1 transcription. In conclusion, TFAP2C-activated MALAT1 modulated the chemoresistance of LUAD cells by sponging miR-200b to upregulate E2F3 and ZEB1. Our findings may provide novel therapeutic targets and perspectives for LUAD treatment., Graphical Abstract

Objective: To study the correlation of blood uric acid level with the degree of anxiety as well as the neurotransmitter and cytokine secretion in young and middle-aged patients with anxiety disorder. Methods: The young and middle-aged patients diagnosed with generalized anxiety disorder in our hospital between March 2015 and February 2018 were selected as the anxiety group, and the healthy subjects receiving physical examination during the same period were selected as the control group. Peripheral blood was collected to determine the contents of uric acid, neurotransmitters and cytokines, and Hamilton Anxiety Scale (HAMA) was adopted to judge the degree of anxiety. Results: The blood uric acid level of anxiety group was obviously higher than that of control group and the higher the HAMA scores, the more significant the rising of blood uric acid levels; serum 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), interleukin-1α (IL-1α), IL-17 and interferon-γ (IFN-γ) contents of anxiety group were significantly higher than those of control group whereas neuropeptide Y (NPY), IL-4 and transforming growth factor-β (TGF-β) contents were significantly lower than those of control group; blood uric acid level of the anxiety group was positively correlated with 5-HT, NE, DA, IL-1α, IL-17 and IFN-γ contents, and negatively correlated with NPY, IL-4 and TGF-β contents. Conclusion: The rise of blood uric acid level in young and middleaged patients with anxiety disorder is related to the aggravation of anxiety degree as well as the abnormal secretion of neurotransmitters and cytokines.

Background Transcription factor forkhead box M1 (FOXM1) is a crucial regulator in colorectal cancer (CRC) progression. However, the regulatory mechanisms causing dysregulation of FOXM1 in CRC remain unclear. Methods Dual-luciferase reporter assay was conducted to determine FOXM1 as miR-6868-5p target. The function of miR-6868-5p and FOXM1 in CRC angiogenesis was verified in vitro. Intratumoral injection model was constructed to explore the effect of miR-6868-5p on angiogenesis in vivo. Chromatin immunoprecipitation assays were used to assess direct binding of H3K27me3 to the miR-6868 promoter. Results Through integrated analysis, we identified miR-6868-5p as the potent regulator of FOXM1. Overexpression of miR-6868-5p in CRC cells inhibited the angiogenic properties of co-cultured endothelial cells, whereas silencing of miR-6868-5p had opposite effects. In vivo delivery of miR-6868-5p blocked tumor angiogenesis in nude mice, resulting in tumor growth inhibition. Rescue of FOXM1 reversed the effect of miR-6868-5p on tumor angiogenesis. Further mechanistic study revealed that FOXM1 promoted the production of IL-8, which was responsible for the miR-6868-5p/FOXM1 axis-regulated angiogenesis. Reciprocally, FOXM1 inhibited miR-6868-5p expression through EZH2-mediated H3K27me3 on miR-6868-5p promoter, thus forming a feedback circuit. Clinically, the level of miR-6868-5p was downregulated in CRC tissues and inversely correlated with microvessel density as well as levels of FOXM1 and IL-8 in tumor specimens. Conclusions Together, these data identify miR-6868-5p as a novel determinant of FOXM1 expression and establish a miR-6868-5p/FOXM1 regulatory circuit for CRC angiogenesis, providing potential target for CRC treatment. Electronic supplementary material The online version of this article (10.1186/s13046-018-0970-5) contains supplementary material, which is available to authorized users.

Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS and established PHF5A as potential therapeutic target., Graphical abstract, Dysregulated alternative splicing is closely associated with oncological processes. Our study revealed that splicing factor PHF5A was associated with poor prognosis of CRC patients and promoted CRC progression by inducing aberrant splicing of TEAD2 to activate YAP signaling. Splicing modulators targeting PHF5A had potent antitumor activity.

// Tao Xie 1, * , Jian Geng 1, * , Ye Wang 1 , Liya Wang 2 , Mengxi Huang 2 , Jing Chen 2 , Kai Zhang 2 , Lijun Xue 2 , Xiaobei Liu 2 , Xiaobei Mao 2 , Yanan Chen 2 , Qian Wang 2 , Tingting Dai 2 , Lili Ren 2 , Hongju Yu 2 , Rui Wang 2 , Longbang Chen 2 , Cheng Chen 1, 2 , Xiaoyuan Chu 1, 2 1 Department of Medical Oncology, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing 210002, China 2 Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China * These authors have contributed equally to this work Correspondence to: Xiaoyuan Chu, email: chuxiaoyuan000@163.com Cheng Chen, email: chencheng1289@126.com Keywords: colorectal cancer, FOXM1, 5-FU, chemoresistance Received: September 07, 2016 Accepted: December 07, 2016 Published: December 29, 2016 ABSTRACT 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for colorectal cancer (CRC). However, frequently occurred 5-FU resistance poses a great challenge in the clinic. Elucidating the underlying mechanisms and developing effective strategies against 5-FU resistance are highly desired. Here we identified the upregulation of FOXM1 in 5-FU nonresponsive CRC patients by gene expression profile analysis and 5-FU-resistant CRC cells by qRT-PCR assay. Silencing of FOXM1 promoted the sensitivity of CRC cells to 5-FU by enhancing cell apoptosis, while overexpression of FOXM1 conferred CRC cells with 5-FU resistance both in vitro and in vivo . Furthermore, we showed that genetic and pharmacological inhibition of FOXM1 resensitized resistant CRC cells to 5-FU treatment. Mechanistically, FOXM1 promoted the transcription of ABCC10 by directly binding to its promoter region. Notably, treatment with ABCC10 inhibitor reversed FOXM1-induced resistance to 5-FU in vivo . Clinical investigation revealed that the levels of FOXM1 and ABCC10 were positively correlated in CRC tissues. Therefore, FOXM1 promotes 5-FU resistance by upregulating ABCC10, suggesting that FOXM1/ABCC10 axis may serve as a potential therapeutic target for 5-FU resistance in CRC patients.

Most of gastric carcinoma (GC) is attributed to infection by Helicobacter pylori (H. pylori) but there is increasing evidence that the positive H. pylori status correlates with better prognosis in GC. The H. pylori-induced cellular immune response may suppress cancer and in this work, recombinant pcDNA3 plasmids encoding various fragments of H. pylori virulence genes of cagA, vacA and babA are constructed and combined into groups to immunize BALB/c mice. The activated splenic CD3(+) T cells are purified and the anticancer effects are investigated in vitro and in vivo. The H. pylori DNA vaccines induce a shift in the response from Th1 to Th2 that mimicks the immune status in patients of GC with chronic H. pylori infection. The stimulated CD3(+) T cells inhibit the growth of human GC cells in vitro and adoptive transfusions of the CD3(+) T cells suppress the growth of GC xenograft in vivo. The effects may be caused by the larger ratios of infiltrated CD8(+)/CD4(+) T cells, reduced infiltration of regulatory FOXP3(+) T cells, and enhanced apoptosis induced by upregulation of Caspase-9/Caspase-3 and downregulation of Survivin. Our results reveal the potential immunotherapeutic value of H. pylori vaccine-activated CD3(+) T cells in those with advanced GC.

In this paper, a similarity transformation is presented to reduce the generalized (3 + 1)-dimensional cubic–quintic nonlinear Schrodinger equation with distributed coefficients to the related constant-coefficients one. Then a number of spatiotemporal self-similar wave solutions are constructed. Under the specific choice of the dispersion, cubic and quintic nonlinearities, phase modulation and the gain/loss, we investigate the dynamical behaviors of those spatiotemporal self-similar waves in an inhomogeneous optical fiber media.

Background The aim of this study was to investigate the association of survivin expression with metastasis of colorectal cancer (CRC). Methods RT-PCR and Western blot assays were performed to detect survivin expression in CRC cells and normal intestinal epithelial cell. The expression of survivin gene was also detected in 15 CRC tissues, surrounding and adjacent colon tissues. Moreover, survivin expression in 48 CRC tissues with or without lymph node metastasis was analyzed. Multivariate analysis for lymph node metastasis was performed using logistic regression model. RNA interference was used to inhibit survivin expression in CRC cells and analyze its effect on invasion and metastasis of CRC cells. Results The expression levels of survivin mRNA and protein were higher in CRC cells than in normal intestinal epithelial cell line. The average levels of survivin mRNA and protein were higher in CRC tissues than surrounding or adjacent colon tissues (P

In this paper, we investigate the detection of single-carrier transmission over frequency selective fading channels with symmetric alpha-stable (SαS) noise. To mitigate the effects of the inter-symbol interference (ISI) cased by multi-path propagation and the destructive impulsive noise, a non-linear myriad filter is firstly adopted and an asymptotic statistic method is then introduced for to analyze the output behavior of the myriad filter. It is found that the output noise of myriad filter in our system is asymptotically normal. Based on this observation, the classic low-complexity minimum mean square error (MMSE) based turbo equalizer (TEQ) is invoked. Substantial performance improvements over the conventional scheme designed for Gaussian channels are observed.

Microstructures and electrical properties of low dielectric constant (low-k) nanoporous silica films, prepared by sol–gel method using hydrofluoric acid (HF) replacing hydrochloric acid (HCl) as catalyst, have been investigated. It is found that the incorporation of HF effectively adjusts the hydrolysis and condensation of the tetraethoxylane based silica sols and makes the surface modification more sufficiently, leading to the increase of the porosity and the change in chemical bonds, and thus significantly improves the electrical properties of the films. The k value of 1.5 is reached in HF catalyzed films, which is much lower than that in HCl ones. The leakage current density are reduced to the lowest value of 6.12×10-9 A/cm2 in HF catalyzed films. It is determined that the Schottky emission occurs in HF catalyzed films, and both Schottky and Poole–Frenkel emissions occur in HCl ones, which may be due to the lower effective oxide charge density near the nanoporous silica and Si interfaces in HF catalyzed films than in HCl ones.

FOXM1, a member of the Forkhead Box (Fox) family of transcription factors, plays a critical role in tumor development and metastasis. The aim of this study was to elucidate its role in colorectal cancer (CRC), particularly prognosis and metastasis. Semi-quantitative RT-PCR and Western blot assays were used to measure the expression levels of FOXM1 mRNA and protein in 15 CRC and adjacent normal mucosa tissues. Immunohistochemical assay was performed to detect FOXM1 protein expression in 112 CRC tissues and further determine its clinicopathological and prognostic significance. RNA interference (RNAi) was used to knockdown endogenous FOXM1 expression in CRC cell lines and to analyze the effects of FOXM1 knockdown on migration and invasion of CRC cells. The relative expression levels of FOXM1 mRNA and protein were significantly higher in CRC tissues than in adjacent normal mucosa tissues (P

In this paper, a similarity transformation is presented to reduce the generalized (3+1)-dimensional (D) nonlinear Schrodinger equation (NLSE) with distributed coefficients to the related constant-coefficients (3+1)D NLSE. Some Jacobi elliptic function solutions are given by a generalized subequation method for the constant-coefficients equation. Thus some general solutions for the generalized (3+1)D NLSE are constructed by the similarity transformation and the Jacobi elliptic function solutions. Some figures are given to illustrate the main evolution properties of these general solutions by computer simulation.

The aim of this study was to investigate the association of survivin expression with metastasis of colorectal cancer (CRC).RT-PCR and Western blot assays were performed to detect survivin expression in CRC cells and normal intestinal epithelial cell. The expression of survivin gene was also detected in 15 CRC tissues, surrounding and adjacent colon tissues. Moreover, survivin expression in 48 CRC tissues with or without lymph node metastasis was analyzed. Multivariate analysis for lymph node metastasis was performed using logistic regression model. RNA interference was used to inhibit survivin expression in CRC cells and analyze its effect on invasion and metastasis of CRC cells.The expression levels of survivin mRNA and protein were higher in CRC cells than in normal intestinal epithelial cell line. The average levels of survivin mRNA and protein were higher in CRC tissues than surrounding or adjacent colon tissues (P 0.05). High survivin expression was an independent factor for predicting lymph node metastasis of CRC (P = 0.043). RNAi-mediated survivin knockdown could significantly inhibit in vitro invasion and in vivo metastasis of CRC cells, which might be inactivation of matrix metalloproteinases.Targeting survivin will be a potential strategy to suppress metastasis of CRC.

Gastric carcinoma (GC) remains one of the most malignant tumors either in morbidity or mortality rates around the world (IARC, 2002). Development of GC is influenced by multiple factors including genetic, biological, social, and psychological ones, etc.., however, the function mechanisms of which are too sophisticated and still under explorations (Matysiak-Budnik & Megraud, 2006). Similar to other malignant tumors, GC leads to death mainly due to system or organ failure because of cancer advancement and metastasis. Chemotherapy-based regimens combined with radiological and immunomodulating therapies are fundamental but unsatisfactory because most GC patients are in advanced stage when diagnosed, although radical operation throws those at early stage a light of prolonged survival and even clinical cure (Quiros & Bui, 2009). As for prophylaxis, many reports have mentioned the protective role of eradication of Helicobacter pylori, which has been identified as a definite carcinogen for GC, but few evidences proved a successful H. pylori vaccine showing effects on GC prevention, just as Hepatitis B virus vaccine on prevention of primary hepatocellular carcinoma (IARC, 1994; Murakami et al., 2005; Cai et al., 2005; Di Bisceglie 2009). H. pylori, a stomach colonizing spiral gram-negative bacterium, interacts with the host in a multiplicity of ways during its adhesion, colonization, invasion, and induction of inflammatory and immune responses (Peek 2005). The great majority of researchers link H. pylori infection with development or even recurrence of GC according to some clinical trials, meta-analyses, and in vitro experiments (Wong et al., 2004; Fukase et al., 2008). However, a few recent studies have disclosed the other side of the coin, in which positive H. pylori status appears to be associated with better outlook in GC patients (Meimarakis et al., 2006; Marrelli et al., 2009). Therefore, H. pylori probably factually play a bi-directional role in GC just like a double-edged sword. To learn about both edges of H. pylori infection will provides us with new sights in vaccine design, prevention, and even therapy of GC. Herein, we try to re-elucidate the relationship between H. pylori and GC from novel angles, in which GC consists of H. pylori-related (Hp-GC) and non-H. pylori-related (nHp-GC) ones

Background Transverse sinus stenosis (TSS) is common among patients with cerebral venous sinus thrombosis. No previous studies have reported on double-track sign detected on axial Gd-enhanced T1WI in TSS. This study aimed to determine the sensitivity and specificity of the double-track sign in the detection of TSS. Methods We retrospectively reviewed medical records of 383 patients with transverse sinus thrombosis (TST) and 30 patients with normal transverse sinus from 5 participating hospitals in china from January 2008 to June 2014. 167 feasible transverse sinuses included in this study were categorized into TSS (n = 76), transverse sinus occlusion (TSO) (n = 52) and transverse sinus normal (TSN) groups (n = 39) according to imaging diagnosis on digital subtraction angiography (DSA) or magnetic resonance venography (MRV). Double-track sign on axial Gd-enhanced T1WI was compared among the three groups. Sensitivity and specificity of double-track sign in detection of TSS were calculated, with final imaging diagnosis of TSS on DSA or MRV as the reference standard. Results Of 383 patients with TST recruited over a 6.5-year period, 128 patients were enrolled in the study, 255 patients were excluded because of insufficient clinical data, imaging finding and delay time, and 30 matched patients with normal transverse sinus were enrolled in the control group. Therefore, double-track sign assessment was conducted in 167 available transverse sinuses of 158 patients. Of the 76 sinuses in TSS group, 51 had double-track sign. Of the other 91 sinuses in TSO and TSN groups, 3 had a false-positive double-track sign. Thus, double-track sign on axial Gd-enhanced T1WI was 67.1% (95% CI 55.3–77.2) sensitive and 96.7% (95% CI 89.9–99.1) specific for detection of TSS. Conclusions The double-track sign on axial Gd-enhanced T1WI is highly specific and moderate sensitive for detection of TSS. Nevertheless, it could be a direct sign and might provide an early clue for TSS.