Transcriptome profiling reveals differential expression of interferon family induced by dengue virus 2 in human endothelial cells on tissue culture plastic and polyacrylamide hydrogel.

A cell model is critical for studying the molecular mechanisms of dengue virus 2 (DENV-2) invasions and cell bioactivity can be easily affected by the substrate matrix. Tissue culture plastic (TCP) and polyacrylamide hydrogel (PAMH) are two kinds of matrices widely used for cells. The effects of different matrices on the cultured cells with DENV-2 invasion remain unknown. To address the issue, the effects of TCP and PAMH were explored in primary human umbilical vein endothelial cells (HUVECs) with DENV-2 invasion. HUVECs were assigned into four groups: group A (cultured on TCP), group B (cultured on PAMH), group C (cultured on TCP with DENV-2 invasion), and group D (cultured on PAMH with DENV-2 invasion). Flow cytometry was performed on HUVECs after 48-hr culture. Gene expression patterns were analyzed by gene microarray. The levels of interleukin-29 (IL-29) were measured by real-time qRT-PCR and ELISA. There were no cell apoptosis induced by DENV-2 in HUVECs cultured on TCP and PAMH (P > 0.05). After DENV-2 invasion, the up-regulated genes involve in the activities of oligoadenylate synthetase (OAS), interferon-related cytokine, and growth factors so on. The up-regulated pathways involve in the responses to DENV-2 and innate immunity. IL-29 was induced in the HUVECs on PAMH when compared with the cells on TCP (P < 0.05). Thus, different matrices cause different immune responses, which should be considered in the cell models for exploring the molecular mechanisms of DENV-induced diseases.

Multibarrier-penetrating drug delivery systems for deep tumor therapy based on synergistic penetration strategy.

Nanotherapies, valued for their high efficacy and low toxicity, frequently serve as antitumor treatments, but do not readily penetrate deep into tumor tissues and cells. Here we developed an improved tumor-penetrating peptide (TPP)-based drug delivery system. Briefly, the established TPP iNGR was modified to generate a linear NGR peptide capable of transporting nanotherapeutic drugs into tumors through a CendR pathway-dependent, neuropilin-1 receptor-mediated process. Although TPPs have been reported to reach intended tumor targets, they often fail to penetrate cell membranes to deliver tumoricidal drugs to intracellular targets. We addressed this issue by harnessing cell penetrating peptide technology to develop a liposome-based multibarrier-penetrating delivery system (mbPDS) with improved synergistic drug penetration into deep tumor tissues and cells. The system incorporated doxorubicin-loaded liposomes coated with nona-arginine (R9) CPP and cyclic iNGR (CRNGRGPDC) molecules, yielding Lip-mbPDS. Lip-mbPDS tumor-targeting, tumor cell/tissue-penetrating and antitumor capabilities were assessed using CD13-positive human fibrosarcoma-derived cell (HT1080)-based in vitro and in vivo tumor models. Lip-mbPDS evaluation included three-dimensional layer-by-layer confocal laser scanning microscopy, cell internalization/toxicity assays, three-dimensional tumor spheroid-based penetration assays and antitumor efficacy assays conducted in an animal model. Lip-mbPDS provided enhanced synergistic drug penetration of multiple biointerfaces for potentially deep tumor therapeutic outcomes.

Comparison of ultrasonic and CO2laser pretreatment methods on enzyme digestibility of corn stover.

To decrease the cost of bioethanol production, biomass recalcitrance needs to be overcome so that the conversion of biomass to bioethanol becomes more efficient. CO(2) laser irradiation can disrupt the lignocellulosic physical structure and reduce the average size of fiber. Analyses with Fourier transform infrared spectroscopy, specific surface area, and the microstructure of corn stover were used to elucidate the enhancement mechanism of the pretreatment process by CO(2) laser irradiation. The present work demonstrated that the CO(2) laser had potential to enhance the bioconversion efficiency of lignocellulosic waste to renewable bioethanol. The saccharification rate of the CO(2) laser pretreatment was significantly higher than ultrasonic pretreatment, and reached 27.75% which was 1.34-fold of that of ultrasonic pretreatment. The results showed the impact of CO(2) laser pretreatment on corn stover to be more effective than ultrasonic pretreatment.

[The efficacy and safety of continuous erythropoietin receptor activator in dialytic patients with chronic renal anemia: an open, randomized, controlled, multi-center trial].

OBJECTIVE: To evaluate the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) once every 4 weeks by subcutaneous administration on hemoglobin (Hb) maintenance in dialytic patients with chronic renal anemia who had been treated with stable dose of erythropoietin (EPO). METHODS: This was an open, randomized, controlled, multi-center trial. All the hemodialysis or peritoneal dialytic patients in EPO maintenance treatment received subcutaneous EPO-ß during the 6-week pre-treatment period to maintain Hb level between 100 g/L and 120 g/L. Eligible patients were randomized (2:1) to accept either C.E.R.A. once every 4 weeks by subcutaneous administration (C.E.R.A. group, n = 187) or subcutaneous EPO-ß 1-3 times weekly (EPO group, n = 94) for 28 weeks (including 20-week dose titration period and 8-week efficacy evaluation period). The starting dose of C.E.R.A. was converted according to the dose of EPO-ß administered in the week preceding the first study drug administration. The primary outcome was the change of Hb level between the baseline and that in the efficacy evaluation period. RESULTS: Totally 253 patients completed the whole 28-week treatment. The change of baseline-adjusted mean Hb was +2.57 g/L for C.E.R.A. group and +1.23 g/L for EPO group, resulting in a treatment difference of 1.34 g/L (95%CI -1.11 - 3.78 g/L). Since the lower limit of 95%CI was greater than the pre-defined non-inferiority margin -7.5 g/L (P < 0.0001), C.E.R.A. once every 4 weeks by subcutaneous administration was clinically non-inferior to EPO regarding the maintenance of stable Hb level. The proportion of patients maintaining Hb level within the range of 100-120 g/L through efficacy evaluation period was similar between the two groups (69.0% for C.E.R.A. group vs 68.9% for EPO group, P > 0.05). The overall incidence of adverse events was similar between the C.E.R.A.(41.7%) and EPO (46.2%) groups (P > 0.05). The safety findings were in accordance with the patients' primary diseases rather than the administration. CONCLUSIONS: Conversion from EPO to C.E.R.A. once every 4 weeks by subcutaneous injection could maintain the Hb in target level in dialytic patients with renal anemia, and it was non-inferior to EPO. In general, subcutaneous administration of C.E.R.A. is well tolerated in dialytic patients with chronic renal anemia.

Oligosaccharide polyester and triterpenoid saponins from the roots of Polygala japonica.

An oligosaccharide polyester, 1-O-(E)-p-coumaroyl-(3-O-benzoyl)-beta-D-fructofuranosyl-(2-->1)-[6-O-(E)-feruloyl-beta-D-glucopyranosyl-(1-->2)]-[6-O-acetyl-beta-D-glucopyranosyl-(1-->3)-(4-O-acetyl)-beta-D-glucopyranosyl-(1-->3)]-4-O-[4-O-alpha-L-rhamnopyranosyl-(E)-p-coumaroyl]-alpha-D-glucopyranoside (polygalajaponicose I), and four triterpenoid saponins, 3beta, 23, 27-trihydroxy-29-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-olean-12-en-28-oic acid (polygalasaponin XLVII), 3-O-beta-D-glucopyranosyl presenegenin 28-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-fucopyranosyl ester (polygalasaponin XLVIII), 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->5)-beta-D-apiofuranosyl-(1-->4)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl ester (polygalasaponin XLIX) and 2beta, 27-dihydroxy-3-O-beta-D-glucopyranosyl 11-oxo-olean-12-en-23, 28-dioic acid 28-O-beta-D-galactopyranosyl-(1-->5)-beta-D-apiofuranosyl-(1-->4)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-fucopyranosyl ester (polygalasaponin L), in addition to five known compounds have been isolated from the roots of Polygala japonica.

[Studies on chemical constituents in root of Isatis indigotica].

OBJECTIVE: To study the chemical constituents in the root of Isatis indigotica. METHOD: The constituents root were separated through various chromatographic techniques and their structures were elucidated by means of physicochemical properties and the analysis of their spectral data. RESULT: Eleven compounds were isolated and identified as (+) -isolariciresinol (1), lariciresinol (2), lariciresinol-9-O-beta-D-glucopyranoside (3), lariciresinol-4'-O-beta-D-glucopyranoside (4), lariciresinol-4,4'-bis-O-beta-D-glucopyranoside (5), 3-formylindole (6), 1-methoxy-3-indolecarbaldehyde (7), 1-methoxy-3-indoleacetonitrile (8), deoxyvasicinone (9), epigoitrin (10), adenosine (11). CONCLUSION: Compounds 4-8 were isolated from I. indigotica for the first time.

[Application of the digital osteotomy template in the mandibular angle osteotomy ].

Objective: To investigate the application of the digital osteotomy template in the mandibular angle osteotomy,so as to increase the precision and symmetry of the osteotomy. Methods: 8 cases were included in our study (female,average age 25.5).The CT data (DICOM format) were reformatted into 3D images using 3D imaging software (ProPlan).The osteotomy lines were designed on digital 3D theoretical model with ProPlan.Then the statistics of the ostectomy were imported into GeoMagic in the form of STL file to design the 3D osteotomy template.The osteotomy template was fabricated with FDA certificated PLA through RP machine. During operation,the template was inserted into operation area to guide the osteotomy.A line was drawn along the edge of ostectomy plate with a grinding ball and osteotomy was done along the curvilinear line using a goose saw. Results: The removed bone proved to be highly matched with the template.All the post-operative results were satisfactory.There were no complications such as fracture,life-threatening hemorrhage and infection.The post-operative measurement showed good symmetry. Conclusions: With the guidance of osteotomy templates,the surgeon can perform the osteotomy in an accurate way.The precision and symmetry of the osteotomy are greatly improved.

[Survey on prevalence of 1 526 children with sleep disturbances in age of 2 to 12 years old in Chengdu].

OBJECTIVE: To find out the prevalence of sleep disturbances for children aged 2 to 12 years old in Chengdu. METHODS: Totally 1 600 children aged 2-12 years old were selected from 5 districts in Chengdu and investigated by using questionnaire. RESULTS: All 1 526 survey papers were returned. The average time of every day sleep in each age group (infant group, pre-school age group and school age group) were 12.12 hours, 10.42 hours and 9.47 hours. The sleep time of the children in those three groups were much less than the standard one. The proportion of the prevalence of sleep disturbance was 37.88%. Among them, there were snoring in 5.57%, choke/gargling in 1.25%, sleep inquietude in 7.86%, mouth breathing in 4.59%, sweating in 21.36%, member spasm in 2.82%, molar teeth in 8.26%, night talking in 4.02%, somnambulate in 0.2%, bedwetting in 1.95%, and difficulty falling asleep in 10.75%. There were significant differences shown in different sexes and ages, and in incidence of symptoms of some sleep disturbances. The affecting factors were the co-sleeping, tonsillitis, bronchitis, pollen allergy and their parent's snore. CONCLUSION: The prevalence of sleep disturbances being higher and more severe than before might be due to the less sleeping time in Chengdu in children aged 2 to 12 years old. More attention should be paid by parents, the Ministry of Education and the children's doctors.

Helical tomotherapy with dynamic running-start-stop delivery compared to conventional tomotherapy delivery.

PURPOSE: Despite superior target dose uniformity, helical tomotherapy(®) (HT) may involve a trade-off between longitudinal dose conformity and beam-on time (BOT), due to the limitation of only three available jaw sizes with the conventional HT (1.0, 2.5, and 5.0 cm). The recently introduced dynamic running-start-stop (RSS) delivery allows smaller jaw opening at the superior and inferior ends of the target when a sharp penumbra is needed. This study compared the dosimetric performance of RSS delivery with the fixed jaw HT delivery. METHODS: Twenty patient cases were selected and deidentified prior to treatment planning, including 16 common clinical cases (brain, head and neck (HN), lung, and prostate) and four special cases of whole brain with hippocampus avoidance (WBHA) that require a high degree of dose modulation. HT plans were generated for common clinical cases using the fixed 2.5 cm jaw width (HT2.5) and WBHA cases using 1.0 cm (HT1.0). The jaw widths for RSS were preset with a larger size (RSS5.0 vs HT2.5 and RSS2.5 vs HT1.0). Both delivery techniques were planned based on identical contours, prescriptions, and planning objectives. Dose indices for targets and critical organs were compared using dose-volume histograms, BOT, and monitor units. RESULTS: The average BOT was reduced from 4.8 min with HT2.5 to 2.5 min with RSS5.0. Target dose homogeneity with RSS5.0 was shown comparable to HT2.5 for common clinical sites. Superior normal tissue sparing was observed in RSS5.0 for optic nerves and optic chiasm in brain and HN cases. RSS5.0 demonstrated improved dose sparing for cord and esophagus in lung cases, as well as penile bulb in prostate cases. The mean body dose was comparable for both techniques. For the WBHA cases, the target homogeneity was significantly degraded in RSS2.5 without distinct dose sparing for hippocampus, compared to HT1.0. CONCLUSIONS: Compared to the fixed jaw HT delivery, RSS combined with a larger jaw width provides faster treatment delivery and improved cranial-caudal target dose conformity. The target coverage achieved by RSS with a large jaw width is comparable to the fixed jaw HT delivery for common cancer sites, but may deteriorate for cases where complex geometry is present in the middle part of the target.

Immobilized heparin and its anti-coagulation effect on polysulfone membrane surface.

Polysulfone has been widely used as hemodialysis membrane material because of its excellent physiochemical performance. There is still a need to further improve its anti-coagulation property in clinical practice. In this work, we covalently immobilized heparin onto polysulfone membrane to improve its anti-coagulation performance. Low temperature plasma technique with environmentally friendly nitrogen as the gas source, as well as N-ethyl-N'-[3-dimethylaminopropy] carbodiimide hydrochloride/hydroxy-2,5-dioxopyrolidine-3-sulfonicacid sodium chemistry were utilized to immobilize heparin onto the surface of polysulfone membrane. X-ray photoelectron spectroscopy, attenuated total reflectance Fourier-transform infrared spectroscopy, as well as water contact angle results confirmed successful binding of heparin to the membrane surface. Only slight permeability differences were observed between the immobilized surface and the unmodified surface, while the polysulfone membrane had become more hydrophilic after immobilization. The blood coagulation time was greatly prolonged after modification and less platelets adhesion was observed on the heparin immobilized surface. Also, compared with heparin injection doses in clinical, the heparinized process in our work consumed less heparin. Our study suggests that the immobilized heparin has local anti-coagulation effect, while reducing the doses.