Search

DNA proficient mismatch repair colon cancer (pMMR CC) is the most common subtype of sporadic CC. We aimed to investigate the role of long noncoding RNAs (lncRNAs) in pMMR CC carcinogenesis. In the present study, we conducted transcriptomic analysis of lncRNAs-mRNAs in five low-grade intraepithelial neoplasia (LGIN), five high-grade intraepithelial neoplasia (HGIN), four pMMR CC, and five normal control (NC) tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway, and coexpression network analyses were performed to elucidate the functions of lncRNAs and mRNAs as well as their interactions. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate five dysregulated lncRNAs in a large set of colon tissues. Receiver-operating characteristic (ROC) curves were employed to evaluate the performance of the candidate lncRNAs. A set of 5783 differentially expressed lncRNAs and 4483 differentially expressed mRNAs were detected among the LGIN, HGIN, pMMR CC, and NC samples. These differentially expressed lncRNAs and mRNAs were assigned to 275 significant GO terms and 179 significant KEGG enriched pathways. qRT-PCR confirmed that the expression of five selected lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, NR_026543, and ENST00000545920) were consistent with the microarray data. ROC analysis showed that four lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, and NR_026543) had larger area under the ROC curve (AUC) values compared to serum carcinoembryonic antigens, thereby distinguishing NC from pMMR CC. In conclusion, several lncRNAs play various roles in the adenoma-carcinoma sequence and may serve as potential biomarkers for the early diagnosis of pMMR CC.

In the present work, approaches of the Computational Fluid Dynamics (CFD) simulation, the Particle Image Velocimetry (PIV) measurement, and the spinning experiment were applied to investigate the phenomenon of air recirculation in blunt-die melt-blown airflow. Firstly, the characteristics of air recirculation were explored by CFD simulation. The simulation results predicted that the air recirculation generated a lateral air velocity along the nose-piece direction. Then, the air circulation was experimental verified by using PIV technique. The PIV results confirmed the predicted conclusions of CFD simulation. Finally, the effect of air recirculation on the microfiber spinning during the melt-blown process was experimentally investigated by a spinning experiment using a blunt die with nose-piece width of 2.56 mm. The spinning results indicated that the air circulation had a tendency of splitting the normal polymeric stream, which played negative effect on the continuity of microfiber spinning. This work is expected to provide some clues to melt-blown die design and the quality control of nonwoven products.

To analyze whether face-to-face education before colonoscopy improves the quality of bowel preparation and increases the detection of adenomas.A retrospective cross-sectional study of adult patients with colorectal polyps identified by colonoscopy as outpatients was performed. The patients underwent an added colonoscopy inpatient for resection of colorectal polyps. As outpatients, we gave the patients written bowel preparation instructions; however, when they were inpatients, we supplied face-to-face education. We analyzed the data from the two colonoscopies of the same group of patients out- and in-patients, including the quality of the intestinal preparation, the time to reach the ileocecal region, and the detection of adenomas.A total of 260 patients {age 63 [56, 68] years old, male/female (169/91)} were retrospectively included in our study. Two hundred fifty-two patients with a total of 685 adenomas were detected, 94 patients with 179 adenomas overlooked in the first colonoscopy. The BBPS Score during inpatient was higher than that during outpatient, {9 [8, 9] vs. 7 [6, 9]}, P0.05, the Bubble Score during inpatient was lower than that during outpatient [0 (0.00, 0.00) vs. 0 (0.00, 1.00)], P0.05. The time to reach the ileocecal region during inpatient is shorter than that during outpatient {6 [5, 9] vs. 7.5 [5, 11] min}, P0.05. Poor bowel preparation, flat adenoma morphology, and adenoma diameter lower than 5mm were related adenoma misdiagnoses, P0.05.Face-to-face patient education can improve the quality of bowel preparation, then shorten the time to reach the ileocecal region, and increase detection of colorectal adenomas.

Unreasonable human activities may cause the accumulation of heavy metals (HMs) in the agricultural soil, which will ultimately threaten the quality of soil environment, the safety of agricultural products, and human health. Therefore, the accumulation characteristics, potential sources, and health risks of HMs in agricultural soils in China’s subtropical regions were investigated. The mean Hg, Cu, Zn, Pb, and Cd concentrations of agricultural soil in Jinhua City have exceeded the corresponding background values of Zhejiang Province, while the mean concentrations of determined 8 HMs were less than their corresponding risk-screening values for soil contamination of agricultural land in China. The spatial distribution of As, Cr, Ni, Cu, and Pb were generally distributed in large patches, and Hg, Zn, and Cd were generally sporadically distributed. A positive definite matrix factor analysis (PMF) model had better performance than an absolute principal component–multiple linear regression (APCS-MLR) model in the identification of major sources of soil HMs, as it revealed higher R2 value (0.81–0.99) and lower prediction error (−0.93–0.25%). The noncarcinogenic risks (HI) of the 8 HMs to adults and children were within the acceptable range, while the carcinogenic risk (RI) of children has exceeded the safety threshold, which needs to be addressed by relevant departments. The PMF based human health risk assessment model indicated that industrial sources contributed the highest risk to HI (32.92% and 30.47%) and RI (60.74% and 61.5%) for adults and children, followed by agricultural sources (21.34%, 29.31% and 32.94% 33.19%). Therefore, integrated environmental management should be implemented to control and reduce the accumulation of soil HMs from agricultural and industrial sources.

The age-related functional exhaustion limits potential efficacy of mesenchymal stem cells (MSC) in treating cardiovascular disease. Therefore, rejuvenation of aged MSC in the elderly population is of great interest. We have previously reported that Erb-B2 receptor tyrosine kinase 4 ( ERBB4) plays a critical role in regulating MSC survival under hypoxia. The aim of this study was to investigate whether ERBB4 rejuvenates aged MSC and how ERBB4 enhances therapeutic efficacy of aged MSC in treating myocardial infarction (MI). Compared with vector aged MSC (aged-MSC), ERBB4-engineered aged MSC (ER4-aged-MSC) conferred resistance to oxidative stress-induced cell death and ameliorated the senescent phenotype in vitro. Four weeks after MI, the ER4-aged-MSC group exhibited enhanced blood vessel density, reduced cardiac remodeling and apoptosis with improved heart function compared with the aged-MSC group. Overexpression of ERBB4 caused an increase in phosphorylated v-akt murine thymoma viral oncogene homolog 1 (AKT), and phosphorylated ERK expression under hypoxia. ER4-aged-MSC secreted higher levels of angiopoietin, epithelial neutrophil activating peptide 78, VEGF, and fibroblast growth factor 2, and enhanced tube formation in HUVEC. The impact of ERBB4 on protein expression, proangiogenesis, cell behavior, and cytokine secretion was abolished by inhibiting PI3K/AKT and MAPK/ERK signaling pathway.-Liang, X., Ding, Y., Lin, F., Zhang, Y., Zhou, X., Meng, Q., Lu, X., Jiang, G., Zhu, H., Chen, Y., Lian, Q., Fan, H., Liu, Z. Overexpression of ERBB4 rejuvenates aged mesenchymal stem cells and enhances angiogenesis via PI3K/AKT and MAPK/ERK pathways.

The protective effects of mesenchymal stem cell (MSC)-based therapy for myocardial infarction (MI) are largely hampered as they age. Apelin is an endogenous ligand of its receptor APJ and plays an essential role in regulating multiple biological activities including MSC proliferation and survival. In this study, we investigated whether Apelin regulates MSC senescence and whether its overexpression could rejuvenate aged MSCs (AMSCs) to improve cardiac protection following infarction in mice. MSC senescence was evaluated by senescence-associated β-galactosidase assays. Apelin level was examined by western blotting. Autophagy was determined by transmission electron microscopy. The cardioprotective effect of AMSCs with Apelin overexpression (Apelin-AMSCs) was assessed in a mouse MI model. Apelin expression was dramatically reduced in AMSCs. Interestingly, knockdown of Apelin induced young MSCs (YMSC) senescence, whereas overexpression rescued AMSC senescence. Apelin overexpression also increased AMSC angiogenic capacity. Mechanistically, Apelin overexpression upregulated the autophagy level of AMSCs by activating AMP-activated protein kinase (AMPK) signaling, thereby rejuvenating AMSCs. Compared with AMSCs, transplantation of Apelin-AMSCs achieved better therapeutic efficacy for MI by enhancing cell survival and angiogenesis. In conclusion, our results reveal that Apelin activates AMPK to rejuvenate AMSCs by increasing autophagy and promotes cardioprotection following infarction in mice. This study identified a novel target to rejuvenate AMSCs and enhance their therapeutic efficacy.

Objective: To investigate the sexual activity of older adults, to understand their knowledge attitude and practice(KAP) regarding sexually transmitted diseases (STD) and to perform correlation analyses of STD symptoms in this population.Methods: A cross-sectional study was conducted among 585 subjects from counties in eastern China. Data was collected from unified questionnaires; descriptive statistics were used for demographic characteristics and sexual activity, which used student t test, to compare the different groups, and multivariate logistic regression analysis to identify the dependence of influential factors.Results: 24.62% of participants were reported as sexually active. The subjects still work and the main income from personal salary was higher than other individuals . Furthermore, when participants monthly income or expenses was more than 1000 RMB, they seemed to have a higher sexual activity. Gender and monthly income were dependent on influential factors related to sexual activity. 54.7% showed good awareness of STD, but only 7.96% of them consistently and correctly used condoms; moreover, 21.03% report to have previously suffered from any STD symptoms. Sexual behavior, use of condoms and commercial sexual behavior were dependent on influential factors of sexual activity.Conclusions: Sexual needs and sexual health of older adults should not be neglected, effective strategies should be drafted for such population.

BackgroundReports indicate that saffron originated from Iran then introduced into mainland China through the earlier established trans-Tibet trade routes in ancient China. Based to the theory of traditional Chinese medicine, saffron functions by promoting blood circulation and removing blood stasis, cooling blood and detoxification, as well as relieving depression for tranquilization. Modern medical research has demonstrated several properties of saffron including antitumor, antidepressant, enhancement of immunity, cardioprotection. Notably, recent studies introduce that saffron has a neuroprotective effect, specifically in the treatment of Parkinson's disease in recent years. Nevertheless, the underlying molecular mechanism remains elusive so far. As such, this study aims to predict the underlying mechanism of saffron on Parkinson's disease through network pharmacology and molecular docking.MethodsA functional-based network pharmacology and molecular docking model was constructed for dissecting the underlying mechanism of saffron on Parkinson's disease. Based on the Traditional Chinese Medicine System Pharmacology database (TCMSP) and the literature reviews, the putative targets of Saffron were collected. Further, the interaction networks of Drug- candidate compounds targets-Therapeutic targets-Disease were mined using the Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted and the String database was used to analyze the protein interaction network. Finally, Molecular docking was used to predict the interaction between the components in Saffron and key targets by MOE 2014.09 software.ResultsA total of 9 candidate compounds from saffron corresponding to 52 therapeutic targets of Parkinson's disease were identified. The neuroprotective effect of saffron in the treatment of PD was attributed to the strong binding between crocin (including crocin I and crocin II) as well as key targets including CASP3, IL6, and MAPK8. Additionally, the auxiliary neuroprotective effects might have originated from quercetin, kaempferol, isorhamnetin, crocetin, safranal, and picrocrocin because of their slightly weaker binding capacity to the key targets.ConclusionSaffron exhibits a synergistic effect via multiple targets and pathways in the treatment of Parkinson's disease and our systemic pharmacological analysis provides a basis for the clinical application and in-depth study of saffron.

Cerebral ischemia and reperfusion is a common pathophysiologic process, which is involved in stroke and brain trauma. Recent studies revealed that activating epidermal growth factor receptor (EGFR) ameliorates cerebral ischemia/reperfusion (I/R) injury, however, the precise mechanisms remain to be illuminated. In this study, the neurological behavior was evaluated by Longa score. The infarct volume was performed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and the expression of p-EGFR, p-STAT3, connexin (Cx43), Bax and Bcl-2 were detected by Western blot. The neurological behavior and infarct volume were increased in rats with cerebral I/R injury. Epidermal growth factor (EGF) pretreatment significantly decreased neurological deficit and infarct volume. However, the antagonist of EGFR, AG1478 attenuated the EGF-induced reduction of neurological deficit and infarct volume. Moreover, the inhibitor of JAK2/STAT3, AG490 undermined the protective effects stimulated by activating EGFR in rats with I/R injury. In addition, EGF pretreatment increased the expression of Bcl-2 and reduced the expression of Bax and Cx43, and the effects were abolished after using AG1478 and AG490. These findings implicate that JAK2/STAT3 pathway plays the vital role in I/R injury protection from activating EGFR. And the neuroprotective effects may associate with inhibiting the Cx43 expression and the inhibition of apoptosis.

Background: Impaired wound healing is a common complication of diabetes and is the leading cause of lower extremity amputation. Treatment with fenofibrate, a peroxisome proliferators–activated receptor α (PPARα) agonist, was associated with a lower risk of amputations, particularly minor amputations without known large-vessel diseases, probably through non-lipid mechanisms. The current study aimed to test our hypothesis that fenofibrate stimulates angiogenesis and restores endothelial precursor cell (EPC) function via inhibiting Nod-like receptor protein 3 (NLRP3) inflammasome in streptozotocin (STZ)-induced diabetic mice. Methods: Male C57BL/6 mice were randomly divided into three groups: control, STZ-induced diabetic mice and fenofibrate treated diabetic group. Wound closure was assessed by wound area and CD31 positive capillaries. Both the migration and tube formation capacities of EPCs were measured. Intracellular nitric oxide (NO) and superoxide (O2-) levels were determined. Activity of NLRP3 inflammasome in EPCs was assessed by measuring thioredoxin-interacting protein (TXNIP), NLRP3, and caspase-1 expression. Results: Compared with the untreated diabetic mice, wound closure and capillary densities were significantly increased in fenofibrate treated group. Fenofibrate treatment restored EPC function, increased NO production, and decreased O2- level in EPCs of diabetic mice. Furthermore, fenofibrate deregulated the activity of NLRP3 inflammasome by reducing TXNIP, NLRP3 and caspase-1 expression in EPCs of diabetic mice. In vitro, fenofibrate prevented high glucose induced EPC dysfunction, deregulated NLRP3 inflammasome activity. In addition, fenofibrate inhibited IL-1β expression caused by combination use of high glucose and lipopolysaccharide. Conclusion: Fenofibrate can accelerate wound healing in diabetic mice, which at least in part was mediated by improving the impaired EPC function via a NLRP3 inflammasome pathway, suggesting the significance of PPARα agonists in the treatment of diabetes.

Introduction: Sixty-three patients with gastric phytobezoars were reviewed. Methods: forty-eight (76.2%) patients received endoscopic combined with chemical therapies and 15 (23.8%) received only chemical therapy initially. Fifty-one (81.0%) patients achieved complete removal (only chemical therapy 14/15), while 12 (19.0%) received further endoscopic therapies. Results: finally, 62 (98.4%) patients achieved a complete removal. Considering only patients with combined treatment as a first approach, treatment success was associated with a softer phytobezoar consistency (p = 0.023). Conclusion: in conclusion, most patients achieve a favorable outcome. Chemical therapy is useful in selected cases. Repeated endoscopic therapies may be needed in order to completely remove phytobezoars with a hard consistency.

Background and aim To evaluate the effectiveness of systematic training in the application of narrow-band imaging (NBI) International Colorectal Endoscopic (NICE) classification for the prediction of the histology of colorectal polyps. Methods This is a single-center study. In total, 260 still images of colorectal polyps from 225 patients were included. Two series of 130 images obtained using NBI and white light without magnification were distributed to 10 endoscopists-five highly experienced endoscopists (HEE group) and five less experienced endoscopists (LEE group)-for assessment using the NICE classification, before and after systematic training. Results Before systematic training, accuracy in both groups was 79.54% and specificity was relatively poor (HEE: 62.46%, LEE: 69.23%, P = 0.297). After systematic training, specificity significantly improved (HEE: 96.61%, LEE: 97.54%, P = 0.000 and P = 0.013, respectively). Accuracy also significantly increased to 94.93% and 96.46% in the HEE and LEE groups, respectively. Sensitivity and negative predictive value did not significantly improve in the post-test; however, both were high in both the pre- and post-test. The κ-values in both groups were excellent (HEE: 0.93, LEE: 0.91). Among the components of the NICE classification, surface pattern yielded the highest performance, whereas color yielded the lowest. Conclusion Systematic, feedback-based, training programs can help achieve high accuracy and good interobserver agreement in the application of the NICE classification for the prediction of the histology of colorectal polyps by endoscopists with different levels of experience.

Background & Aims Aging is one of the risk factors of non-alcoholic fatty liver disease (NAFLD). Yet, the mechanism underlying the aging-associated NAFLD-like syndrome is not fully understood. Nicotinamide adenine dinucleotide (NAD), a ubiquitous coenzyme, has protective effects against aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of aging-induced NAFLD. Methods NR supplemented food (2.5 g/kg food) was applied to aged mice for three months while normal chow to the other groups. Body weight, food intake, liver weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammatory infiltration. Results NR repletion significantly reduced fat pat mass in aged mice, while not altered the body weight, food intake, and liver weight. NR repletion significantly rescued the NAD reduction in aged mice. The total cholesterol and triglyceride levels could be lowered by NR repletion in aged mice. The AST level was also significantly reduced by NR repletion in aged group, while the ALT level lowered but without significance. Notably, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis could be markedly corrected by NR repletion. In addition, Kupffer cells accumulated and inflammatory infiltration could also be remarkably reversed by NR repletion in aged mice. Conclusion Aging was associated with NAFLD-like phenotypes in mice, which could be reversed by oral NR repletion. Therefore, oral NR uptake might be a promising strategy to halt the progression of NAFLD.

Choices of bicycle and trip chain are important decisions in an individual's daily travel activities. Little is known about the causal relationship between the two decisions. It is interesting to ask if a decision on bicycle choice is made prior to the determination on a trip chain, or is dependent on the pre-determined chain pattern. This study aims to explore the relationship between the choices of bicycle and trip chain and capture the order of decision between them. Based on the survey data from a medium-sized Chinese city, the co-evolutionary approach with logit-modeling framework was estimated for the study purpose. Results show that there are more bicycle uses in the subsistence trip chains as compared to these non-subsistence ones. Considering the interaction between the two decisions improves the predicting accuracy of both bicycle choice and chain choice. In most cases, a trip chain is determined prior to a decision on bicycle choice, especially when the chain contains subsistence activities. For travelers who currently using a bicycle, most of them first decide the chain type and then choose a bicycle accordingly. Most of travelers who first determine the trip mode do not consider using a bicycle. We also estimate a model to predict the decision process of travelers. The order of decision is mainly impacted by the individual and household characteristics as well as the travel attributes. Findings of this study are discussed to assist the development of policies to promote cycling in urban areas.

3D Laser-rapid Prototyping blisk blades could have more defects, like slag inclusions, cracks and incomplete fusions, than ones made by traditional machining. Therefore, a six-axis automated ultrasonic testing system (AUTS) was developed for 3D laser-rapid prototyping blisk blades in this paper. The applied technology is mainly about B-spline surface reconstruction from CAD, scan path planning based on B-spline surface and adaptive defect gating. In experiments conducted on blades with the system, defects could be clearly identified on generated 3D C-Scan images.