Ultrahigh packing density next generation microtube array membrane: A novel solution for absorption-based extracorporeal endotoxin removal device.

Sepsis is a deadly disease that is widely attributed to endotoxin released by gram-negative bacterial infections often plague emergency care facilities. Conventionally antibiotics and vasopressors are used to treat this disease. Recent treatment protocol shifted to a membrane to remove the offending endotoxin monomer. Despite this shift, membrane-based devices are often extremely costly, hindering accessibility to this life saving medical device. In view of this challenges, we adopted the internally developed polysulfone (PSF) microtube array membrane alternating (MTAM-A) for use in blood sepsis treatment. PSF MTAM-A were with polymyxin B (PMB) molecules immobilized were assembled into an internally developed cartridge housing and subjected to endotoxin removal models with water and blood spiked with 100 EU/ml of endotoxin as the feed solution. Samples were derived at 15, 30, 60, and 120 min and endotoxin levels were determined with limulus amebocyte lysate assay and benchmarked against the commercially available Toraymyxin device. The PSF MTAM-A with 2.3 times the surface area was successfully fabricated and with PMB molecules immobilized, and assembled into a hemoperfusion device. Dynamic endotoxin removal test revealed and overall endotoxin removal capacity of 90% and a superior endotoxin removal efficiency that was significantly higher than that of Toraymyxin (internally conducted and reported). The data suggested that PSF MTAM-A PMB membranes could potentially be applied in future hemoperfusion devices which would be significantly more efficient, compact, and affordable; potentially making such a life-saving medical device widely available to the general public.

Microtube Array Membrane (MTAM)-Based Encapsulated Cell Therapy for Cancer Treatment.

The treatment of cancer has evolved significantly in recent years with a strong focus on immunotherapy. Encapsulated Cell Therapy (ECT) for immunotherapy-based anti-cancer treatment is a unique niche within this landscape, where molecules such as signaling factors and antibodies produced from cells are encapsulated within a vehicle, with a host amount of benefits in terms of treatment efficacy and reduced side effects. However, traditional ECTs generally lie in two extremes; either a macro scale vehicle is utilized, resulting in a retrievable system but with limited diffusion and surface area, or a micro scale vehicle is utilized, resulting in a system that has excellent diffusion and surface area but is unretrievable in the event of side effects occurring, which greatly compromises the biosafety of patients. In this study we adapted our patented and novel electrospun Polysulfone (PSF) Microtube Array Membranes (MTAMs) as a 'middle' approach to the above dilemma, which possess excellent diffusion and surface area while being retrievable. Hybridoma cells were encapsulated within the PSF MTAMs, where they produced CEACAM6 antibodies to be used in the suppression of cancer cell line A549, MDA-MB-468 and PC 3 (control). In vitro and in vivo studies revealed excellent cell viability of hybridoma cells with continuous secretion of CEACAM6 antibodies which suppressed the MDA-MB-468 throughout the entire 21 days of experiment. Such outcome suggested that the PSF MTAMs were not only an excellent three-dimensional (3D) cell culture substrate but potentially also an excellent vehicle for the application in ECT systems. Future research needs to include a long term in vivo >6 months study before it can be used in clinical applications.

Mononuclear and trinuclear DyIII SMMs with Schiff-base ligands modified by nitro-groups: first triangular complex with a N-N pathway.

Using two Schiff-base ligands containing an electron-withdrawing group (NO2), we obtained two mononuclear and two trinuclear complexes with the general formula [Dy(hni)(NO3)(DMF)2]·DMF (1·DMF), [Dy(hni)2(H2O)2]·NO3·EtOH (2·NO3·EtOH), [Dy3(hnc)3(DMF)6] (3) and [Gd3(hnc)3(DMF)6] (4) (H-hni: 2-(hydroxyl-3-methoxy-5-nitrophenyl)methylene(isonictino)hydrazine and H3-hnc: 1,5-bis(2-hydroxy-3-methoxy-5-nitrobenzylidene)carbonohydrazide). Four complexes were confirmed by infrared spectroscopy and single-crystal X-ray diffraction. The crystal structure of complex 3 reveals that the modified Schiff-base ligand provides two different tridentate coordination pockets (ONN and ONO) to encapsulate DyIII with a unique N-N pathway. The magnetic properties of all four complexes have been investigated using dc and ac susceptibility measurements. The frequency-dependent ac susceptibility is indicative of single-molecule magnetic behavior without and/or with an optimum dc field with a relaxation barrier Ueff = 34 K (400 Oe), 19 K (0 Oe) and 80 K (0 Oe) for complexes 1, 2 and 3, respectively.

Role of interleukin-21 and interleukin-21 receptor polymorphisms in the treatment of HBeAg-positive chronic hepatitis B patients with peginterferon.

The aim of this study was to evaluate the relationship between interleukin-21 (IL-21) and interleukin-21 receptor (IL-21R) polymorphisms and the response to peginterferon alfa (PEG-IFN α) therapy in HBeAg-positive chronic hepatitis B (CHB) patients.A total of 143 HBeAg-positive CHB patients treated for 48 weeks with PEG-IFN α and followed up for 24 weeks post-treatment were retrospectively evaluated. Genotypes analysis was performed for IL-21 polymorphisms rs907715, rs2221903, and IL-21R polymorphisms rs3093301 and rs2285452. Serum IL-21 levels were measured by enzyme-linked immunosorbent assay.The end of virological response (EVR) rate was 46.9% (67/143) at the end of treatment, the sustained virological response (SVR) rate was 43.4% (62/143) and the complete response (CR) rate was 32.1% (46/143) at 24 weeks post-treatment. Patients who carried IL-21 rs 2221903 genotype AA had a rather higher rate of EVR (response rate: 52.4%, odds ratio [OR] 0.42, 95% confidence interval [CI]: 0.19-0.91, P = .021), SVR (response rate: 47.6%, OR 0.43, 95% CI: 0.19-0.95, P = .028), and CR (response rate: 38.1%, OR 0.31, 95% CI: 0.12-0.79, P = .014) when compared to those had AG genotype. Meanwhile, IL-21rs 2221903 genotype AA was also independently associated with markedly reduced HBsAg levels (>1og10 IU/mL) after 24 weeks treatment and low HBsAg levels (<100 IU/mL) at the end of treatment. IL-21 rs907715 AG/GG genotype was independently associated with SVR (OR: 2.92, 95% CI: 0.98-8.6, P = .039; OR: 3.23, 95% CI: 1.0-10.4, P = .039). Patients with IL-21 rs907715 AG/GG genotype had higher serum IL-21 levels than those with rs907715 AA genotype (P = .021).IL-21 rs2221903 and rs907715 polymorphisms were significantly associated with the treatment response to PEG-IFN α among Chinese HBeAg-positive CHB patients.

Synthesis of novel polyhydroxylated pyrrolidine-triazole/-isoxazole hybrid molecules.

A straightforward synthesis of novel, 2-heterocyclyl polyhydroxylated pyrrolidines is described. Stereocontrolled additions of nucleophiles to cyclic nitrones generated the corresponding 2,3-trans adducts, allowing the synthesis of the corresponding pyrrolidines via key intermediates bearing an alkyne and a nitrile oxide. Three hybrid systems, including a pyrrolidine with two isoxazoles and one triazole, are efficiently prepared via 1,3-dipolar cycloaddition. Biological testing of the product alkaloids showed that subtle structural variations have drastic effects on their inhibitory activities against glucosidases.

Effect of binocular vision in myopia and hyperopia amblyopia / 国际眼科杂志(Guoji Yanke Zazhi)

AlM:To investigate the visual function in myopia and hyperopia amblyopia whose corrected visual acuity have recovered to normal.METHODS: The visual function of children ( 50 cases ) with amblyopia eyes by binocular vision correction after treatment above 0. 9 was checked. The simultaneous perception, fusion range and distance stereopsis were measured. According to the refractive condition of the children who were divided into group A ( myopia, 20 cases ) and group B ( hyperopia, 30 cases ) . The statistically difference of simultaneous perception, fusion function and stereopsis in two groups was analyzed. RESULTS: Fifteen ( 75%) and twenty - six ( 87%) children got the simultaneous perception in group A and group B respectively, and the differences between two groups were not significant (χ2=0. 454,P>0. 05). Group A had six children ( 30%) and group B had only seven children (23%) with the normal aggregative fusion range, two groups did not show any difference (χ2 =0. 565, P>0. 05). Respectively sixteen (80%),and twenty children ( 67%) had the normal divided fusion range in group A and group B, the recovery rate did not show any significant difference (χ2=0. 740, P>0. 05). Fifteen (50%) and seven ( 35%) patients acquired the far stereoscopic vision in group B and group A respectively, the recovery rate also did not show any significant difference. Normal distance stereopsis of 50 cases had 22 cases ( 44%) , and normal near stereopsis of 50 cases had 13cases ( 26%) Seven (23%) and 6 (30%) children got the normal near stereoscopic vision in group B and group A respectively, and the recovery rate did not show any significant difference (χ2=0. 195, P>0. 05;χ2=0. 295, P>0. 05).CONCLUSlON:After amblyopia treatment, although the children got the normal visual acuity, the binocular vision still can not completely normal in the short term. Myopia and hyperopia factor will not produce significant effect on binocular vision development.

[The application of integrated surveillance system for symptoms in surveillance of influenza among children].

OBJECTIVE: To explore the integrated application of sales of child-specific over-the-counter (OTC) cold related medications in retail pharmacies and healthcare visits of children for influenza-like illness (ILI) in surveillance and early warning of influenza among children. METHODS: An integrated surveillance system (ISS) was implemented since 2012 in Qianjiang County, a rural area in Hubei Province of China. The daily information from August 1, 2012 to February 28, 2013 of health care visits of children for ILI reported by 80 health facilities and sales of 14 child-specific over-the-counter (OTC) cold related medications reported by 11 pharmacies were extracted from ISS database. Cumulative sums (CUSUM) model was conducted to analyze the degree of fitting and the early warning signal generated; the correlationship was then analyzed further. RESULTS: In 212 days, 983 visits of children for ILI and 12 819 sales by person of child-specific OTC were reported. Conducting CUSUM model, the fitting degree was in the acceptable range, 31 warning signals were generated from ILI data series with 3 peak periods and 14 from OTC data series with 2 peak periods. A similar time trend of two data series was observed with a correlation(r = 0.497, P < 0.05), but without any spatial clustering. And the optimal correlation(r = 0.505, P < 0.05) appeared at a time offset of 4 days preceded by OTC sales. CONCLUSION: The availability of integrated surveillance system for symptoms could be applied for surveillance of influenza among children; while it could explore the possibility of real epidemic in the very early stage.

Comparison of neutralizing and hemagglutination-inhibiting antibody responses for evaluating the seasonal influenza vaccine.

Evaluation of the efficacy of influenza vaccines is essential for vaccine development. This study evaluated the neutralizing and hemagglutination-inhibition antibody response in subjects receiving the 2006-07 and 2007-08 seasonal influenza vaccines. ELISA-based microneutralization demonstrated a greater mean-fold increase and seroconversion rate than the hemagglutination-inhibition assay. The increase in the antibody titers against influenza H1 were higher than those against influenza H3 and influenza B, indicating that the H1 vaccine strain in the 2006-07 and 2007-08 seasons was more immunogenic. These data suggest that the neutralizing antibody response is a better measurement of influenza vaccine efficacy.

Fabrication and characterization of poly(gamma-glutamic acid)-graft-chondroitin sulfate/polycaprolactone porous scaffolds for cartilage tissue engineering.

The development of blended biomacromolecule and polyester scaffolds can potentially be used in many tissue engineering applications. This study was to develop a poly(gamma-glutamic acid)-graft-chondroitin sulfate-blend-poly(epsilon-caprolactone) (gamma-PGA-g-CS/PCL) composite biomaterial as a scaffold for cartilage tissue engineering. Chondroitin sulfate (CS) was grafted to gamma-PGA, forming a gamma-PGA-g-CS copolymer with 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide (EDC) system. The gamma-PGA-g-CS copolymers were then blended with PCL to yield a porous gamma-PGA-g-CS/PCL scaffold by salt leaching. These blended scaffolds were characterized by (1)H NMR, ESCA, water-binding capacity, mechanical test, degradation rate and CS assay. The results showed that with gamma-PGA-g-CS as a component, the water-binding capacity and the degradation rate of the scaffolds would substantially increase. During a 4 week period of culture, the mechanical stability of gamma-PGA-g-CS/PCL scaffolds was raised gradually and chondrocytes were induced to function normally in vitro. Furthermore, a larger amount of secreted GAGs was present in the gamma-PGA-g-CS/PCL matrices than in the control (PCL), as revealed by Alcian blue staining of the histochemical sections. Thus, gamma-PGA-g-CS/PCL matrices exhibit excellent biodegradation and biocompatibility for chondrocytes and have potential in tissue engineering as temporary substitutes for articular cartilage regeneration.