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Objective: To investigate the role of Glucagon-like peptide-2 (GLP-2) in the central nervous system eukaryotic protein kinase (EPK) signal transduction pathway of mice with vascular dementia., Materials and Methods: We take the 3-week-old mice raised in the laboratory as the object of study in this research and then divide them into four groups in random, including sham operation group, control group, GLP-2 group, and GLP-2+ERK (extracellular-signal-regulated kinase) inhibitor intervention group, with 30 in each group. The step-down test, water-maze test, electron microscopy observation, immunohistochemical method, and Western-blotting are adopted to investigate the role of GLP-2 in the central nervous system EPK signal transduction pathway of mice with vascular dementia., Results: The step-down test, as well as the water-maze learning and memory test, shows that the mice injected with GLP-2 in the experiment group have their learning and memory ability improved significantly when compared with other three groups, which is greatly different from that of other three groups (p < 0.05); the electron microscopy observation shows that the injection of GLP can partially reverse the reduction of vesicles while ERK inhibitor removes the said protection; the immunohistochemical result and image analysis result show that the EPK expression quantity in GLP-2 group has no significant difference from that of other three groups (p > 0.05). However, the content of pi-EPK in the GLP-2 group is significantly higher than that in VD group and GLP-2+PD98095 group and is significantly different from them (p < 0.05), and such result is in line with the result of Western-blotting., Conclusions: GLP can influence the change in hippocampus cells extensions and finally influence their cognitive function by activating the EPK signal transduction pathway of hippocampal neuron in the central nervous system.

Previous studies report controversial role of Hedgehog (HH) signaling in the progression of colon cancer. This study aimed to investigate the expressions of smoothened (SMO) and downstream glioma-associated oncogene homology-1 (GLI1) in colon cancer, colonic adenoma and normal tissues. Colon cancer and normal tissue samples were collected from 49 patients with colon cancer while colonic adenoma tissue samples were obtained from 34 patients with colonic adenoma. Then the expressions of SMO and GLI1 were investigated using immunohistochemistry (IHC). For the detection of SMO and GLI1 expression, IHC staining results indicated that SMO was mainly expressed on the membrane while GLI1 was mainly expressed in the cytoplasm. The positive rates of SMO and GLI1 protein expressions were significantly increased in colon cancer tissue and colonic adenoma tissue when compared with normal colon tissue. In contrast, the significant difference was not found in the positive rates of SMO and GLI1 protein expressions between colon cancer tissue and colonic adenoma tissue. More importantly, it was found that SMO and GLI1 expressions possibly increased gradually from the normal colon to colonic adenoma to the colon cancer. Furthermore, no distinct correlations were detected between the expression levels of SMO and GLI1 and clinicopathological parameters, including age, gender, differentiation and Dukes stage. The present results provided some new information to the possible role of HH signaling in colon cancer progression. SMO and GLI1 maybe suggested asbiomarkers to identify colon cancerous, precancerous and normal tissues as well astherapeutic targets for colon cancer treatment.

Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury.

B7-H4 is member of the B7 family that negatively regulates the immune response, which are important for fine-tuning of the tumor microenvironment. Dysregulation of B7-H4 expression has been associated with tumor progression. However, expression level of B7-H4 in hepatocellular carcinoma (HCC) tissues is still a controversial topic. In addition, whether serum B7-H4 expression of HCC patients has any clinical value is unknown. We compared serum levels of B7-H4 in patients with HCC and healthy controls by using the ELISA method. Association between serum B7-H4 expression level and clinical parameters of HCC was further investigated. Log-rank test and Kaplan-Meier method were employed to evaluate the overall survival rate of HCC patients. Univariate and multivariate analysis of prognostic factors were performed with the Cox regression model. Our results showed that HCC patients had significantly higher serum B7-H4 level as compared with healthy controls (P < 0.001). In addition, serum B7-H4 expression was correlated with HCC clinical parameters including serum AFP expression and TNM stage. HCC patients in the higher serum B7-H4 expression group had a poorer 5-year overall survival rate (P = 0.028). Moreover, serum B7-H4 expression was shown to be an independent prognostic factor for HCC (P = 0.034). The findings from this study suggest that serum B7-H4 is an independent prognostic indicator for HCC and may be a promising biomarker for early diagnosis as well as disease prognosis of HCC.

The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.

Lipid derivatives of nucleoside analogs and their nanoassemblies have become the research hotspot due to their unique function in cancer therapy. Six lipid derivatives of 3'-hydroxyurea-deoxythymidine were prepared with zidovudine as the raw material. The 5'-substituted lipid chains in the derivatives were from the various fatty acids including octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid and octadecanoic acid corresponding to the derivatives OHT, DHT, DDHT, TDHT, HDHT and ODHT. The amphiphilic derivatives formed Langmuir monolayers at the air/water interface with different surface pressure-molecular area isotherms depending on the length of lipid chains. The nanoassemblies of OHT, DHT, DDHT, TDHT and HDHT and the nanoscale precipitates of ODHT were obtained after we injected their tetrahydrofuran solutions doped with hydrophilic long chained polymers into water. Electron microscopy showed that the morphology of nanoassemblies may be vesicles or nanotubes depending on the length of lipid chains. The shorter the lipid chains were, the softer the nanoassemblies. Computer simulation supported the experimental results. The nanoassemblies and the nanoscale precipitates showed much higher anticancer effects on SW620 cells than the parent drug hydroxyurea. The nanostructures of the derivatives are promising anticancer nanomedicines., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To study the damage on organs from salt sensitivity hypertension or non-salt-sensitive hypertension and the selection of drug combination., Methods: 120 hypertensive patients including 60 cases salt-sensitive (SS) and 60 non-salt-sensitive (NSS) groups were selected in our hospital and their salt load tested. These two groups were randomly divided into two groups, each group with 30 patients, one was given felodipine and perindopril and the others were given indapamide sustained release tablets and perindopril to facilitate the 12-week treatment. Before and after the treatment, patients were tested for physiological indicators, such as sitting blood pressure, 24-hour ambulatory blood pressure, insulin resistance index, comparing changes of various sub-index etc., Results: Significantly different were seen in indices as fasting blood glucose and serum creatinine (P < 0.01), fasting insulin, left ventricular mass index, urinary albumin, body mass index, insulin resistance indices, while between the SS group and the NSS group (P < 0.05). In the SS group, when patients with various sub-indicators were using perindopril combined with indapamide treatment, the related detected indicators tended to be normal and with statistically significant differences (P < 0.05). In the NSS group, those related indexes also tended to be more normal when using felodipine combined with perindopril. However, there were statistically significant differences between the two groups (P < 0.05)., Conclusion: On SS hypertensive patients with target organ damages, perindopril and indapamide seemed to be more effective in NSS patients, indicating that the use of perindopril and felodipine combination, seemed to be more suitable.

Objectives: Our goal was to study the ability of mesenchymal stem cells (MSCs) to stimulate liver regeneration after partial hepatectomy in rats., Methods: MSCs were isolated from bone marrow and cultured in vitro. Their characteristics were analyzed by flow cytometry. After 70% partial hepatectomy, Sprague-Dawley rats were randomly divided into three groups: a control group that was injected with saline, animals that received bone marrow-derived MSCs (BM-MSCs) by tail vein injection (the BM-MSC-TV group) and animals that received BM-MSCs by portal vein injection (the BM-MSC-PV group). The injected BM-MSCs were traced by labeling with 4',6-diamidino-2-phenylindole, and cell proliferations were determined by immunohistochemical staining with Ki-67 and 5-bromo-2'-deoxyuridine., Results: After the third passage, the cultured BM-MSCs had a fibroblast-like morphology and expressed high levels of stem cell markers CD29 and CD90. The levels of albumin rose significantly in the BM-MSC-TV and BM-MSC-PV groups compared with the control group. The number of 4',6-diamidino-2-phenylindole-positive liver cells in the BM-MSC-PV group was significantly higher than in the BM-MSC-TV group. The levels of Ki-67 and 5-bromo-2'-deoxyuridine were significantly higher in the BM-MSC-TV and the BM-MSC-PV groups than in the controls., Conclusion: Taken together, these results indicate that BM-MSC injections enhance liver regeneration after partial hepatectomy in rats., (Copyright © 2013 S. Karger AG, Basel.)

By deviating the nanodisk from the center in the silver nanocrescent/nanodisk structure, we find that the dipole, quadrupole and octupole modes can all induce very high local electric field enhancement (LFE, more than 750) for the coupling of nanocrescent and crescent gap modes, which makes the resonant wavelengths of the non-concentric nanostructures change from the visible to near infrared regions. In addition, the LFE factor of the quadrupole mode is more than 1000, which is suitable for single molecular detection by local surface enhanced spectroscopy.

Objective: To study the chemical constituents of Arachniodes exilis., Methods: The methanolic extract was isolated and purified by silica gel, C18 reverse phase silica gel and Sepadex LH-20 gel column chromatography. The chemical structures were elucidated on the basis of the physicochemical properties and spectral data., Results: Eight phenolic compounds were obtained and identified as aspidin-BB (I), 4-methyl-2-butyl-3,5-dihydroxyphenol (II ), eriodictyol (III), epicatechin (IV), procyanidin B2 (V), miscathoside (VI), eriodictyol-7-O-beta-D-glucopyranuronide (VII), luteolin-4'-O-beta-D-glucopyranuronide (VIII), respectively., Conclusion: Compounds II-VIII are obtained from this plant for the first time.

Objective: To analyze risk factors in patients receiving mechanical ventilation in intensive care unit (ICU)., Methods: The study group consisted of 42 patients receiving mechanical ventilation for longer than 7 days. The general condition, primary diseases, the vital signs before ventilation, accessory examination, acute physiology and chronic health evaluation II (APACHE II) score, and the time of tracheostomy were collected. The patients were divided into two groups of deceased or survived when the mechanical ventilation was weaned. Comparative analysis of all the data was made with Logistic multiple regression., Results: Of the patients enrolled in the study, 22 (52.4%) survived and 20 (47.6%) died in the ICU. Difference in clinical data between death group and survival group was significant (P<0.05). In death group, the APACHE II score, the pressure adjusted heart rate (PAR), the level of blood urea nitrogen (BUN) were higher (all P<0.01), while the level of plasma albumin (ALB), the level of hematocrit (HCT) value, the amount of platelets (PLT) were lower (P<0.05 or P<0.01), and the time of tracheostomy was later compared with those of survival group (P<0.05). There were no significant differences in the time of mechanical ventilation, white blood cells (WBC) and incidence of ventilator-associated pneumonia (VAP) between two groups (all P>0.05). With Logistic multiple regression analysis, the time of tracheostomy, the levels of HCT value, the amount of PLT were correlated with requirement of long-term mechanical ventilation (LTMV) (P<0.05 or P<0.01)., Conclusion: The time of tracheostomy, the levels of HCT value, the amount of PLT were independent risk factors associated with patients requiring LTMV.

The authors achieved the temporal coherent control in an Er(3+)-doped telluride glass, one kind of disordered solids. The upconversion at 670 nm was modulated and the dephasing time was simulated as 300 fs. Moreover, the photon echo signal gave the dephasing time due to the phonon interaction. The agreement between the two data indicates that the interaction between the wavepacket and the phonon leads to the fast disappearance of wavepackets interference, which is helpful for the technique to be applied to the disordered solids.

Objective: To observe the changes of L929 cell membrane with atomic force microscope (AFM) after infrasound exposure and to explore the mechanisms of effect of infrasound on cell membrane., Methods: After primary culture, the L929 cells were exposed to infrasound with intensity output of 130 dB and frequency of 16 Hz 2 hours each day for 3 days. The subsequent changes in the membrane of the control cells and the cells exposed to the infrasound were determined by nano-scale scanning with AFM., Results: After infrasound exposure, the normal prominence of the membrane became short and the dent became shallow in the 7.5 microm x 7.5 microm and 4.0 microm x 4.0 microm photographs. The prominence appeared as cobblestones. The surface of the membrane became smooth., Conclusion: The membrane structure of the L929 cells can be changed by infrasound exposure with intensity of 130 dB and frequency of 16 Hz. The change might be one of the characteristics of effect of infrasound on cell membrane.

Though there is ongoing public concern on potential hazards and risk of electromagnetic radiation, the bioeffects mechanism of electromagnetic fields remains obscure. Heart is one of the organs susceptive to electromagnetic fields (EMF). This study was designed to assess the influence of high power pulse microwave and electromagnetic pulse irradiation on cardiomyocytes, to explore the critical mechanism of electromagnetic fields, and to explain the regular course of injury caused by exposure to pulse EMF. Cultured cardiomyocytes were irradiated by high power pulse microwave and electromagnetic pulse first, then a series of apparatus including atom force microscope, laser scanning confocal microscope and flow cytometer were used to examine the changes of cell membrane conformation, structure and function. After irradiation, the cardiomyocytes pulsated slower or stop, the cells conformation was abnormal, the cells viability declined, and the percentage of apoptosis and necrosis increased significantly (P< 0.01). The cell membrane had pores unequal in size, and lost its penetration character. The concentration of Na+, K+, Ca2+, Cl-, Mg2+, Ca2+ and P3+ in cell culture medium increased significantly (P< 0.01). and the concentration of Ca2+ in cells ([Ca2+]i) decreased significantly (P<0.01). The results indicated that cardiomyocytes are susceptible to non-ionizing radiation. Pulse electromagnetic field can induce cardiomyocytes electroporation, and can do great damage to cells conformation, structure and function. Electroporation is one of the most critical mechanisms to explain the athermal effects of electromagnetic radiation.

Objective: To observe the three-dimensional morphological changes on the membrane surface of primary cultured rat hippocampal neurons in response to kainic acid (KA) exposure., Methods: After isolation and primary culture, Wistar rat hippocampal neurons were treated with KA at the concentrations of 0, 25, and 250 micromol/L for different durations (10 and 100 min) to observe the subsequent changes in the membrane surface structure of the neurons by nano-scale scanning with an atomic force microscope (AFM)., Results: Normal neurons displayed smooth membrane surface with even and regular undulation, while the neurons treated with KA, in contrast, presented degenerative changes characterized by cell swelling and coarse membrane surface with processes and holes. As the treatment was prolonged and KA concentration increased, the changes became more evident., Conclusion: As a result of the toxic effect of KA, the membrane surface ultrastructure of rat hippocampal neurons undergo obvious changes, which can be clearly observed and quantitatively analyzed by means of AFM.

Amino acids and small peptides with different steric configurations and lipophilicities were appended to dopamine. Eighteen compounds have been synthesized. The attachment of D-amino acids or N-methyl amino acids onto the dopamine molecule caused a marked decrease in cardiovascular activity by intravenous injection, while the introduction of lipophilic amino acids caused a marked increase in myocardial contractility and blood pressure in anesthetized dogs. The durations of action were also prolonged.