Vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2 (Flk-1/KDR), play a key role in tumor angiogenesis. Blocking the VEGF-VEGFR-2 pathway may inhibit tumor growth. Here, we used human VEGFR-2 as a model antigen to explore the feasibility of immunotherapy with a plasmid DNA vaccine based on a xenogeneic homologue of this receptor.

Evidence from behavioral, electrophysiological and diffusion-weighted imaging studies suggest that schizophrenia patients suffer from deficiencies in bilateral brain communication, and this disruption may be related to the occurrence of auditory verbal hallucinations (AVH). To increase our understanding of aberrant inter-hemispheric communication in relation to AVH, we recruited two groups of first-episode schizophrenia patients: one group with AVH (N = 18 AVH patients) and one without hallucinations (N = 18 Non-AVH patients), and 20 healthy controls. All participants received T1 structural imaging and resting-state fMRI scanning. We adopted a newly developed index, voxel-mirrored homotopic connectivity (VMHC), to quantitatively describe bilateral functional connectivity. The whole-brain VMHC measure was compared among the three groups and correlation analyses were conducted between symptomology scores and neurological measures. Our findings suggest all patients shared abnormalities in parahippocampus and striatum. Aberrant bilateral connectivity of default mode network (DMN), inferior frontal gyrus and cerebellum only showed in AVH patients, whereas aberrances in superior temporal gyrus and precentral gyrus were specific to Non-AVH patients. Meanwhile, inter-hemispheric connectivity of DMN correlated with patients' symptomatology scores. This study corroborates that schizophrenia is characterized by inter-hemispheric dysconnectivity, and suggests the localization of such abnormalities may be crucial to whether auditory verbal hallucinations develop.

The prognostic nutritional index (PNI) has been reported to correlate with the prognosis in patients with various malignancies. We performed a meta-analysis to determine the predictive potential of PNI in digestive system cancers. Twenty-three studies with a total of 7,384 patients suffering from digestive system carcinomas were involved in this meta-analysis. A lower PNI was significantly associated with the shorter overall survival (OS) [Hazard Ratio (HR) 1.83, 95% Confidence Interval (CI) 1.62-2.07], the poorer disease-free survival (DFS) (HR 1.85, 95% CI 1.19-2.89), and the higher rate of post-operative complications (HR 2.31, 95% CI 1.63-3.28). In conclusion, PNI was allowed to function as an efficient indicator for the prognosis of patients with digestive system carcinomas.

A variety of structural abnormalities have been described in post traumatic stress disorder (PTSD), but only a few studies have focused on cortical thickness alterations in recent onset PTSD. In this study, we adopted surface-based morphometry (SBM), which enables an exploration of global structural changes throughout the brain, in order to compare cortical thickness alterations in recent onset PTSD patients, trauma-exposed subjects but without PTSD, and normal controls. Moreover, we used region of interest (ROI) partial correlation analysis to evaluate the correlation among PTSD symptom severity and significant changes of cortical thickness. The widespread cortical thickness reduction relative to the normal controls were found in bilateral inferior and superior parietal lobes, frontal lobes, hippocampus, cingulate cortex, and right lateral occipital lobes in trauma survivors, whereas cortical thickness was only increased in left calcarine cortex in PTSD group. The average cortical thickness of hippocampus and cingulate cortex decreased by 10.75% and 9.09% in PTSD, 3.48% and 2.86% in non PTSD. We further demonstrated that the cortical thicknesses of bilateral ACC and PCC, superior frontal lobes, and hippocampus are negatively correlated with CAPS scores in all trauma survivors. Our study results suggest that stress widens cortical thinning regions and causes more serious effect in recent onset PTSD than non PTSD. It also shows that the cortical thinning in recent onset PTSD predicts the symptom severity.

The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) and non-RCTs was to evaluate the efficacy and safety of gabapentin versus placebo for pain control after total knee arthroplasty (TKA).In December 2015, a systematic computer-based search was conducted in the Medline, Embase, PubMed, Cochrane Controlled Trials Register (CENTRAL), Web of Science, Google, and Chinese Wanfang databases. This systematic review and meta-analysis were performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria. The primary endpoint was the visual analogue scale (VAS) score after TKA with rest or mobilization at 24 and 48 hours, representing the efficacy of pain control after TKA. Cumulative morphine consumption via patient controlled anesthesia (PCA) was also assessed to determine the morphine-spare effect. Complications such as dizziness, pruritus, vomiting, nausea, and sedation were also compiled to assess the safety of gabapentin. Stata 12.0 software was used for the meta-analysis. After testing for publication bias and heterogeneity across studies, the data were aggregated for random-effects modeling whenever necessary.Six studies involving 769 patients met the inclusion criteria. Our meta-analysis revealed that gabapentin resulted in superior pain relief compared to the control group in terms of VAS score with rest at 24 hours (mean difference [MD] = -3.47; 95% confidence interval [CI] -6.16 to -0.77; P = 0.012) and at 48 hours postoperatively (MD = -2.25; 95% CI -4.21 to -0.30; P = 0.024). There was no statistically significant difference between the groups with respect to the VAS score at 24 hours postoperatively (MD = 1.05; 95% CI -3.31 to 5.42; P = 0.636) or at 48 hours (MD = 1.71; 95% CI -0.74 to 4.15; P = 0.171). These results indicated that the perioperative administration of gabapentin decreases the cumulative morphine consumption via PCA at 24 hours (MD = -8.28; 95% CI -12.57 to -3.99; P = 0.000) and 48 hours (MD = -4.50; 95% CI -10.98 to -3.61; P = 0.221). Furthermore, gabapentin decreased the rate of postoperative dizziness (relative risk [RR], 0.68; 95% CI 0.47-0.99, P = 0.044) and the occurrence of pruritus (RR, 0.50; 95% CI 0.37-0.67, P = 0.000).Based on the current meta-analysis, gabapentin exerts an analgesic and opioid-sparing effect in acute postoperative pain management without increasing the rate of dizziness and pruritus.

Familial risk plays a significant role in the etiology of schizophrenia (SZ). Many studies using neuroimaging have demonstrated structural and functional alterations in relatives of SZ patients, with significant results found in diverse brain regions involving the anterior cingulate cortex (ACC), caudate, dorsolateral prefrontal cortex (DLPFC), and hippocampus. This study investigated whether unaffected relatives of first episode SZ differ from healthy controls (HCs) in effective connectivity measures among these regions. Forty-six unaffected first-degree relatives of first episode SZ patients-according to the DSM-IV-were studied. Fifty HCs were included for comparison. All subjects underwent resting state functional magnetic resonance imaging (fMRI). We used stochastic dynamic causal modeling (sDCM) to estimate the directed connections between the left ACC, right ACC, left caudate, right caudate, left DLPFC, left hippocampus, and right hippocampus. We used Bayesian parameter averaging (BPA) to characterize the differences. The BPA results showed hyperconnectivity from the left ACC to right hippocampus and hypoconnectivity from the right ACC to right hippocampus in SZ relatives compared to HCs. The pattern of anterior cingulate cortico-hippocampal connectivity in SZ relatives may be a familial feature of SZ risk, appearing to reflect familial susceptibility for SZ.

This study explored the associations between common PSCA single-nucleotide polymorphisms (rs2294008, rs2978974, and rs2976392) and breast cancer among 560 breast cancer cases and 583 controls (Chinese Han women). We found rs2294008 was significantly associated with a high risk of breast cancer (homozygote model, odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.06-2.59; recessive, OR: 1.64, 95% CI: 1.06-2.53). And stratification by menopausal status revealed an association of the minor allele of rs2294008 with breast cancer risk among premenopausal (homozygote model, OR: 2.41, 95% CI: 1.03-5.66; recessive, OR: 2.80, 95 % CI: 1.21-6.47) and postmenopausal women (allele model, OR: 1.29, 95% CI: 1.01-1.65). Rs2978974 influenced the breast cancer risk among postmenopausal women in heterozygote model (OR: 1.47, 95% CI: 1.05-2.07). When stratified by clinicopathologic features, the T allele of rs2294008 was associated with progesterone receptor status (homozygote model, OR: 1.98, 95% CI: 1.08-3.63; recessive, OR: 1.87, 95% CI: 1.04-3.37), and the rs2976392 polymorphism was associated with high lymph node metastasis risk in homozygote model (OR: 2.09, 95%CI: 1.01-4.31). Further haplotype analysis suggested that Trs2294008 Ars2976392 Grs2978974 haplotype enhances breast cancer risk (OR:1.52, 95%CI:1.23-1.89, P<0.001). Therefore, among Chinese Han women, the PSCA rs2294008, rs2978974, and rs2976392 minor alleles are associated with increased breast cancer risk especially in progesterone receptor positive breast cancer patients, with breast cancer risk in postmenopausal women, and with high lymph node metastasis risk, respectively. Moreover, Trs2294008 Ars2976392 Grs2978974 haplotype was associated with significantly increased risk of breast cancer.

Metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and the increasing amount of evidences suggest that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in colorectal cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of MACC1 overexpression on clinicopathological features and survival outcomes in colorectal cancer. PubMed, CNKI, and Wanfang databases were searched for relevant articles published update to December 2015. Correlation of MACC1 expression level with overall survival (OS), disease-free survival (DFS), and clinicopathological features were analyzed. In this meta-analysis, fifteen studies with a total of 2,161 colorectal cancer patients were included. Our results showed that MACC1 overexpression was significantly associated with poorer OS and DFS. Moreover, MACC1 overexpression was significantly associated with gender, localization, TNM stage, T stage, and N stage. Together, our meta-analysis showed that MACC1 overexpression was significantly associated with poor survival rates, regional invasion and lymph-node metastasis. MACC1 expression level can serve as a novel prognostic factor in colorectal cancer patients.

Classical dendritic cells (cDCs), monocytes, and plasmacytoid DCs (pDCs) arise from a common bone marrow precursor (macrophage and DC progenitors [MDPs]) and express many of the same surface markers, including CD11c. We describe a previously uncharacterized zinc finger transcription factor, zDC (Zbtb46, Btbd4), which is specifically expressed by cDCs and committed cDC precursors but not by monocytes, pDCs, or other immune cell populations. We inserted diphtheria toxin (DT) receptor (DTR) cDNA into the 3' UTR of the zDC locus to serve as an indicator of zDC expression and as a means to specifically deplete cDCs. Mice bearing this knockin express DTR in cDCs but not other immune cell populations, and DT injection into zDC-DTR bone marrow chimeras results in cDC depletion. In contrast to previously characterized CD11c-DTR mice, non-cDCs, including pDCs, monocytes, macrophages, and NK cells, were spared after DT injection in zDC-DTR mice. We compared immune responses to Toxoplasma gondii and MO4 melanoma in DT-treated zDC- and CD11c-DTR mice and found that immunity was only partially impaired in zDC-DTR mice. Our results indicate that CD11c-expressing non-cDCs make significant contributions to initiating immunity to parasites and tumors.

Cotton fibers are single-celled seed trichomes and provide an ideal model for studying plant cell patterning. At present, the molecular mechanisms of fiber differentiation and initiation are unclear. To determine the proteins involved in these processes, a comparative proteomic analysis based on 2-DE and MS/MS technology was conducted between the fuzzless-lintless mutant (fl) and its parental wild type (WT). Forty-six differentially expressed proteins were identified in ovules at -3 and 0 days post-anthesis (DPA), at the times of cotton fiber differentiation and initiation, respectively. Most of the proteins (72%) were expressed at lower levels in the fl mutant than in the WT, suggesting deleterious effects of the mutant genes on ovule development. The consistency between protein levels and transcript levels was examined using quantitative PCR. The differentially expressed proteins had diverse putative functions related to redox homeostasis, stress responses, post-transcriptional and post-translational regulation, and carbohydrate, energy, protein, amino acid, and sterol metabolism. A strong burst of ROS was detected on the surface of -3 and -2 DPA fl ovules, and the concentrations of several carbohydrates at 0 DPA were lower in the fl mutant than in the WT ovules. These findings suggest that ROS homeostasis may be a central regulatory mechanism for cotton fiber morphogenesis and that post-transcriptional and post-translational regulation may be pivotal in this process.

It has been reported that 80% of all breast carcinoma cases are invasive ductal carcinoma (IDC), and 45% to 78% of invasive breast carcinoma cases are associated with ductal carcinoma in situ (DCIS). Therefore, it is important to gain insights into transcriptome changes that occur during DCIS progression to IDC.

Oral cancer remains a deadly disease worldwide. Lymph node metastasis and invasion is one of the causes of death from oral cancer. Elucidating the mechanism of oral cancer lymph node metastasis and identifying critical regulatory genes are important for the treatment of this disease. This study aimed to identify differentially expressed genes (gene signature) and pathways that contribute to oral cancer metastasis to lymph nodes. The GSE70604-associated study compared gene profiles in lymph nodes with metastasis of oral cancer to those of normal lymph nodes. The GSE2280-associated study compared gene profiles in primary tumor of oral cancer with lymph node metastasis to those in tumors without lymph node metastasis. There are 28 common differentially expressed genes (DEGs) showing consistent changes in both datasets in overlapping analysis. GO biological process and KEGG pathway analysis of these 28 DEGs identified the gene signature CCND1, JUN and SPP1, which are categorized as key regulatory genes involved in the focal adhesion pathway. Silencing expression of CCND1, JUN and SPP1 in the human oral cancer cell line OECM-1 confirmed that those genes play essential roles in oral cancer cell invasion. Analysis of clinical samples of oral cancer found a strong correlation of these genes with short survival, especially JUN expression associated with metastasis. Our study identified a unique gene signature - CCND1, JUN and SPP1 - which may be involved in oral cancer lymph node metastasis.

To elucidate the veritable relationship between three hMLH1 polymorphisms (rs1800734, rs1799977, rs63750447) and cancer risk, we performed this meta-analysis based on overall published data up to May 2017, from PubMed, Web of knowledge, VIP, WanFang and CNKI database, and the references of the original studies or review articles. 57 publications including 31,484 cancer cases and 45,494 cancer-free controls were obtained. The quality assessment of six articles obtained a summarized score less than 6 in terms of the Newcastle-Ottawa Scale (NOS). All statistical analyses were calculated with the software STATA (Version 14.0; Stata Corp, College Station, TX). We found all the three polymorphisms can enhance overall cancer risk, especially in Asians, under different genetic comparisons. In the subgroup analysis by cancer type, we found a moderate association between rs1800734 and the risk of gastric cancer (allele model: OR = 1.14, P = 0.017; homozygote model: OR = 1.33, P = 0.019; dominant model: OR = 1.27, P = 0.024) and lung cancer in recessive model (OR = 1.27, P = 0.024). The G allele of rs1799977 polymorphism was proved to connect with susceptibility of colorectal cancer (allele model: OR = 1.21, P = 0.023; dominate model: OR = 1.32, P <0.0001) and prostate cancer (dominate model: OR = 1.36, P <0.0001). Rs63750447 showed an increased risk of colorectal cancer, endometrial cancer and gastric cancer under all genetic models. These findings provide evidence that hMLH1 polymorphisms may associate with cancer risk, especially in Asians.

Primary hepatic carcinoma is a common malignant tumor with poor treatment efficacy. The effect and mechanism of miR-143 in apoptosis of liver carcinoma cells were investigated in the present study. In vitro transfection of liver carcinoma SMMC-7721 cells was performed using artificially synthesized miR-143 mimics. The proliferation of liver carcinoma cells that were treated was detected by MTT assay. Liver carcinoma cells were then stained using the Annexin V-FITC/PI method, and the apoptosis of stained liver carcinoma cells was measured using a flow cytometer. The relative mRNA expression of NF-κB p65 in the intervention and control groups was assayed using reverse transcription-quantitative polymerase chain reaction, and the protein expression of NF-κB p65 was detected using western blot analysis. The results showed that, in the intervention group, the proliferation rate of cells transfected using miR-143 mimics was significantly lower than that in the control group, the number of apoptotic SMMC-7721 cells in the intervention group increased, and the protein expression of NF-κB p65 was decreased. Thus, miR-143 may downregulate the protein expression of NF-κB p65, thereby triggering the NF-κB signaling transduction pathway inducing apoptosis of liver carcinoma cells.

Polycystic ovary syndrome (PCOS) is a complex gynecological endocrine disease commonly occurred in women of childbearing age. The main hallmark of PCOS includes elevated androgen production and insulin resistance (IR). Liuwei Dihuang Pills (LWDH Pills), a commonly prescribed traditional Chinese medicine (TCM) is widely used as a tonic prescription to treat diabetes, female menopause syndrome and other symptoms with'Kidney-Yin' deficiency. It has been reported the effects LWDH pills on PI3K/Akt signaling pathway in T2DM treatment. Recent studies have also indicated that the treatment of menopausal syndrome may be associated with the ovarian sexual hormone levels regulated by LWDH pills to alleviate female infertility. However, its potential benefits on PCOS have not been fully elucidated.

A meta-analysis was carried out to further evaluate the relationship between ALDH2 Glu487Lys polymorphism and esophageal cancer risk.

High drug resistance, poor water solubility, short half-life, and low local drug concentration are obstacles for successful delivery of chemotherapeutic drugs for lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary delivery is proposed. However, use of NPs is limited by the particle size range for pulmonary drug delivery considering that NPs cannot be deposited directly into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs) will result in suitable particle sizes and retain the advantages of nanodrugs after redispersion when applied in pulmonary delivery. We report the development of novel NPs in the form of PMs loaded with paclitaxel (PTX) and quercetin (QUE) double drugs based on the synthesis of oleic acid-conjugated chitosan (OA-CTS) for pulmonary delivery. This approach is aimed toward prolonging PTX retention time in the presence of QUE and bypassing P-glycoprotein drug efflux pumps. NPs loaded with PTX or QUE were prepared with 11% substitution degree using OA-CTS as the carrier by ionic cross-linking method, which NPs loaded with PTX or QUE were used in the preparation of PMs by spray-drying. The diameters of the PMs ranged from 1 to 5 μm which had uniform size range. Scanning electron microscopy showed that PMs were polymers formed by a large number of NPs and readily redispersed (after redispersion, size of NPs ranged between 250 and 350 nm) in water within 1 h. PMs displayed slow-release characteristics at pH 4.5 and 7.4. The in vivo pharmacokinetic and biodistribution studies suggested that PMs exhibit prolonged circulation time and a markedly high accumulation in the lung. The obtained results indicate that PMs can serve as a promising pulmonary delivery system for combined pharmacotherapy using hydrophobic anticancer drugs.

Secondary metabolites are bioactive substances with diverse chemical structures. Depending on the ecological environment within which they are living, higher plants use different combinations of secondary metabolites for adaptation (e.g., defense against attacks by herbivores or pathogenic microbes). This suggests that the similarity in metabolite content is applicable to assess phylogenic similarity of higher plants. However, such a chemical taxonomic approach has limitations of incomplete metabolomics data. We propose an approach for successfully classifying 216 plants based on their known incomplete metabolite content. Structurally similar metabolites have been clustered using the network clustering algorithm DPClus. Plants have been represented as binary vectors, implying relations with structurally similar metabolite groups, and classified using Ward's method of hierarchical clustering. Despite incomplete data, the resulting plant clusters are consistent with the known evolutional relations of plants. This finding reveals the significance of metabolite content as a taxonomic marker. We also discuss the predictive power of metabolite content in exploring nutritional and medicinal properties in plants. As a byproduct of our analysis, we could predict some currently unknown species-metabolite relations.

Metabolic syndrome (MetS) and its components are associated with increased risks of several cancers. However, the relationship between MetS and upper tract urothelial carcinoma (UTUC) has never been investigated before.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide, with high incidence and poor survival rates. Increased expression of microRNA-205-5p (miR-205-5p) may influence the outcomes of HNSCC, but the identities of miR-205-5p target genes and the potential signaling pathways related to HNSCC remain unclear. RT-qPCR was used to detect the expression levels of miR-205-5p in the plasma of patients with HNSCC. We also performed a meta-analysis using data from relevant literature, and the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases to evaluate the expression level of miR-205-5p in HNSCC. Next, we predicted the potential miR-205-5p target genes in HNSCC. We also used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for enrichment analyses adapted to investigate the dynamics and possible mechanisms of miR-205-5p in HNSCC. Lastly, we predicted the potential miR-205-5p target genes by evaluating their expression level and using Spearman analysis. Expression of miR-205-5p was higher in HNSCC tissues compared to normal unafflicted tissue samples (P < 0.05), and the corresponding summary receiver operating characteristic (sROC) was 0.82.The pooled sensitivity, specificity, PLR, NLR, and DOR values were 0.78 (95% CI: 0.75-0.81), 0.67 (95% CI: 0.60-0.73), 2.34 (95% CI: 1.45-3.76), 0.34 (95% CI: 0.19-0.60), and 8.16 (95% CI: 4.01-16.64), respectively. Based on GO and KEGG analyses, we found that miR-205-5p was correlated with the progression of HNSCC through association with signaling pathways, including the drug metabolism-cytochrome P450 pathway. Analysis of the target genes revealed that flavin-containing monooxygenase isoform 2 (FMO2) and alcohol dehydrogenase 1B (ADH1B) may be important targets of miR-205-5p. In summary, miR-205-5p may have a significant role in the prognosis of HNSCC and may serve as a potential biomarker in HNSCC.