The nucleoside analog 4'-fluorouridine suppresses the replication of multiple enteroviruses by targeting 3D polymerase.

Human enteroviruses are the major pathogens causing hand-foot-and-mouth disease in infants and young children throughout the world, and infection with enterovirus is also associated with severe complications, such as aseptic meningitis and myocarditis. However, there are no antiviral drugs available to treat enteroviruses infection at present. In this study, we found that 4'-fluorouridine (4'-FlU), a nucleoside analog with low cytotoxicity, exhibited broad-spectrum activity against infections of multiple enteroviruses with EC50 values at low micromolar levels, including coxsackievirus A10 (CV-A10), CV-A16, CV-A6, CV-A7, CV-B3, enterovirus A71 (EV-A71), EV-A89, EV-D68, and echovirus 6. With further investigation, the results indicated that 4'-FlU directly interacted with the RNA-dependent RNA polymerase of enterovirus, the 3D pol, and impaired the polymerase activity of 3D pol, hence inhibiting viral RNA synthesis and significantly suppressing viral replication. Our findings suggest that 4'-FlU could be promisingly developed as a broad-spectrum direct-acting antiviral agent for anti-enteroviruses therapy.

Superhydrophilic polyethersulfone (PES) membranes with high scale inhibition properties obtained through bionic mineralization and RTIPS.

Reverse thermally induced separation (RTIPS) was used to obtain a separation membrane with a better internal structure for a higher water flux and a surface that could easily form a hydration layer. In comparison to the traditional modification method, this work focused on the aspect that the internal structure obtained by changing the membrane-making method provided easier adhesion conditions for the dopamine/TiO2 hybrid nanoparticles (DA/TiO2 HNPs) obtained by biomimetic mineralization. It provided a basis for exploring the variation in adhesion with the water bath temperature and the amount of titanium added through the study of turbidity point, SEM images, water contact angle, thermogravimetric test, EDX, AFM, XPS, FTIR and other test results. The SEM images proved that the membrane obtained through the RTIPS method had a porous surface and spongy internal structure, furthermore, additional polymers were adsorbed. Use of EDX demonstrated that biomimetic mineralization prevented the production of agglomerated titanium dioxide. XPS and FTIR spectra confirmed the introduction and immobilization of HNP aggregation. Moreover, a decrease in the surface roughness and water contact angle further suggested an improvement in the hydrophilicity of the modified membrane. The introduction of HNP at a higher water bath temperature helped increase the water flux up to ten times, moreover, the oil-water separation efficiency could still reach over 99.50%. Lastly, a cycle test of the modified membrane under the optimal conditions helped confirm that the membrane forming conditions at this time could provide a better environment for the formation of the hydrophilic layer, which was conducive to the recycling of the separation membrane. In summary, more fixed more hydrophilic particles could be obtained through the RTIPS method based on biomimetic mineralization to prevent the accumulation of titanium dioxide, thus helping improve permeability and anti-fouling of the membrane.

Development of hydrophilic PES membranes using F127 and HKUST-1 based on the RTIPS method: Mitigate the permeability-selectivity trade-off.

In this study, to mitigate the permeability-selectivity trade-off effect, Pluronic F127 (F127) and HKUST-1 were employed to construct high-performance membranes based on the reverse thermally induced phase separation (RTIPS) method. F127, as a hydrophilic modifier, was applied to increase permeability and resist polyethersulfone (PES) membrane fouling, while the collapse of HKSUT-1 caused by its instability in pure water improved the permeability and selectivity of the membrane. Characterizations demonstrated the successful synthesis of HKUST-1, together with the successful introduction of HKSUT-1 and F127 in PES membranes. It was observed that the membrane prepared by the RTIPS process possessed a uniformly porous surface and sponge-like cross-section with excellent mechanical properties, higher permeability, and selectivity compared to the dense skin and finger-like cross-section of the membrane prepared by the nonsolvent induced phase separation (NIPS) method. Moreover, the permeation and bovine serum albumin (BSA) rejection rate of the optimal membrane reached 2378 L/m2 h and 89.3%, respectively, which were far higher than those of the pure membrane. Hydrophilic F127 and many microvoids formed by the collapse of HKUST-1, played an important role in excellent antifouling properties, high permeability, and selectivity by pure water flux (PWF), flux recovery rate (FRR), BSA flux, and COD removal rate tests. Overall, the membrane with F127 and HKSUT-1 prepared via the RTIPS method not only obtained excellent antifouling properties but also mitigated the permeability-selectivity trade-off.

Drug-loaded PLGA-mPEG microparticles as treatment for atopic dermatitis-like skin lesions in BALB/c mice model.

This study evaluated the feasibility of mizolastine-loaded microparticles as therapy for atopic dermatitis. Microparticles have been researched for decades as a controlled-release drug delivery system, but seldom been used as treatment for skin disease. In this research, we induced dermatitis in BALB/c mice model by repeated topical application of dinitrofluorobenzene and compared the mizolastine microparticles injection and daily mizolastine injection treatment. The results showed that the mizolastine microparticles treatments significantly inhibited ear thickness and dermatitis index in dermatitis model compared with the dermatitis mice without treatment, showing a similar curative effect compared with daily mizolastine injection treatment, and the improvement continued for several days. Inflammatory cells infiltration into the ears and the plasma level of immunoglobulin E were also suppressed by mizolastine microparticles according to the histopathology analysis. In conclusion, the results suggested that drug-loaded microparticles could be a proper candidate for the treatment of skin diseases.

PLGA/liposome hybrid nanoparticles for short-chain ceramide delivery.

PURPOSE: Rapid premature release of lipophilic drugs from liposomal lipid bilayer to plasma proteins and biological membranes is a challenge for targeted drug delivery. The purpose of this study is to reduce premature release of lipophilic short-chain ceramides by encapsulating ceramides into liposomal aqueous interior with the aid of poly (lactic-coglycolicacid) (PLGA). METHODS: BODIPY FL labeled ceramide (FL-ceramide) and BODIPY-TR labeled ceramide (TR-ceramide) were encapsulated into carboxy-terminated PLGA nanoparticles. The negatively charged PLGA nanoparticles were then encapsulated into cationic liposomes to obtain PLGA/liposome hybrids. As a control, FL-ceramide and/or TR ceramide co-loaded liposomes without PLGA were prepared. The release of ceramides from PLGA/liposome hybrids and liposomes in rat plasma, cultured MDA-MB-231 cells, and rat blood circulation was compared using fluorescence resonance energy transfer (FRET) between FL-ceramide (donor) and TR-ceramide (acceptor). RESULTS: FRET analysis showed that FL-ceramide and TR-ceramide in liposomal lipid bilayer were rapidly released during incubation with rat plasma. In contrast, the FL-ceramide and TR-ceramide in PLGA/liposome hybrids showed extended release. FRET images of cells revealed that ceramides in liposomal bilayer were rapidly transferred to cell membranes. In contrast, ceramides in PLGA/liposome hybrids were internalized into cells with nanoparticles simultaneously. Upon intravenous administration to rats, ceramides encapsulated in liposomal bilayer were completely released in 2 min. In contrast, ceramides encapsulated in the PLGA core were retained in PLGA/liposome hybrids for 4 h. CONCLUSIONS: The PLGA/liposome hybrid nanoparticles reduced in vitro and in vivo premature release of ceramides and offer a viable platform for targeted delivery of lipophilic drugs.

Noninvasive fluorescence resonance energy transfer imaging of in vivo premature drug release from polymeric nanoparticles.

Understanding in vivo drug release kinetics is critical for the development of nanoparticle-based delivery systems. In this study, we developed a fluorescence resonance energy transfer (FRET) imaging approach to noninvasively monitor in vitro and in vivo cargo release from polymeric nanoparticles. The FRET donor dye (DiO or DiD) and acceptor dye (DiI or DiR) were individually encapsulated into poly(ethylene oxide)-b-polystyrene (PEO-PS) nanoparticles. When DiO (donor) nanoparticles and DiI (acceptor) nanoparticles were coincubated with cancer cells for 2 h, increased FRET signals were observed from cell membranes, suggesting rapid release of DiO and DiI to cell membranes. Similarly, increased FRET ratios were detected in nude mice after intravenous coadministration of DiD (donor) nanoparticles and DiR (acceptor) nanoparticles. In contrast, another group of nude mice i.v. administrated with DiD/DiR coloaded nanoparticles showed decreased FRET ratios. Based on the difference in FRET ratios between the two groups, in vivo DiD/DiR release half-life from PEO-PS nanoparticles was determined to be 9.2 min. In addition, it was observed that the presence of cell membranes facilitated burst release of lipophilic cargos while incorporation of oleic acid-coated iron oxide into PEO-PS nanoparticles slowed the release of DiD/DiR to cell membranes. The developed in vitro and in vivo FRET imaging techniques can be used to screening stable nanoformulations for lipophilic drug delivery.

Polymeric curcumin nanoparticle pharmacokinetics and metabolism in bile duct cannulated rats.

The objective of this study was to compare the pharmacokinetics and metabolism of polymeric nanoparticle-encapsulated (nanocurcumin) and solvent-solubilized curcumin formulations in Sprague-Dawley (SD) rats. Nanocurcumin is currently under development for cancer therapy. Since free, unencapsulated curcumin is rapidly metabolized and excreted in rats, upon intravenous (i.v.) administration of nanocurcumin only nanoparticle-encapsulated curcumin can be detected in plasma samples. Hence, the second objective of this study was to utilize the metabolic instability of curcumin to assess in vivo drug release from nanocurcumin. Nanocurcumin and solvent-solubilized curcumin were administered at 10 mg curcumin/kg by jugular vein to bile duct-cannulated male SD rats (n = 5). Nanocurcumin increased the plasma Cmax of curcumin 1749 fold relative to the solvent-solubilized curcumin. Nanocurcumin also increased the relative abundance of curcumin and glucuronides in bile but did not dramatically alter urine and tissue metabolite profiles. The observed increase in biliary and urinary excretion of both curcumin and metabolites for the nanocurcumin formulation suggested a rapid "burst" release of curcumin. Although the burst release observed in this study is a limitation for targeted tumor delivery, nanocurcumin still exhibits major advantages over solvent-solubilized curcumin, as the nanoformulation does not result in the lung accumulation observed for the solvent-solubilized curcumin and increases overall systemic curcumin exposure. Additionally, the remaining encapsulated curcumin fraction following burst release is available for tumor delivery via the enhanced permeation and retention effect commonly observed for nanoparticle formulations.

Temperature-sensitive star-shaped block copolymers hydrogels for an injection application: phase transition behavior and biocompatibility.

A series of star-shaped poly(D,L-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (PLGA-mPEG) block copolymers with varying PLGA/mPEG block weight ratios, mPEG block length, and arm numbers were synthesized and phase transition behaviors were investigated. Phase transition characteristics, such as critical gel concentration (CGC) and critical gel temperature (CGT), were closely related to the molecular structure of the star-shaped block copolymers. The CGC was mainly determined by the balance of hydrophobic PLGA and hydrophilic mPEG block (PLGA/mPEG block ratio). The CGTs showed a stronger dependence on mPEG block length and arm number. Also, the CGTs can be adjusted by adding mPEG homopolymer additives. The weight fraction of mPEG had a stronger influence on the CGT values than molecular weight of mPEG. In addition, the MTT assay and histological observations confirmed the acceptable biocompatibility of the star-shaped block copolymer. Hence, the star-shaped PLGA-mPEG block copolymer was a promising candidate as a novel injectable gel.

Does the Choice of Operative Side Affect the Clinical Outcome of Unilateral Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fracture?

BACKGROUND: Studies have found that the rate of improvement in pain after percutaneous kyphoplasty (PKP) is 49% to 90%, and there are still some patients who may continue to sustain intractable back pain after surgery. OBJECTIVES: To compare the clinical efficacy and imaging results between unilateral PKP performed from the symptom-dominating side and the non-dominating side in OVCF treatment. STUDY DESIGN: Prospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: One hundred forty-two patients of osteoporotic vertebral compression fracture (OVCF) treated with unilateral PKP were eventually recruited and randomly assigned to either the A or B group. Patients in group A received PKP from the symptom-dominating side; patients in group B received PKP from the symptom non-dominating side. The demographic characteristics, related surgical information, and complications observed within both groups were recorded. The clinical outcomes evaluation included the visual analog scale (VAS) score for low back pain and the Oswestry Disability Index (ODI). Evaluation of imaging results included anterior height (AH), kyphosis angulation (KA), and contralateral distribution rate of bone cement. RESULTS: One hundred eighteen patients (48 men and 70 women; age range: 60-83 years), including 59 patients in the A group and 59 patients in the B group, were available for the complete assessment. There were 5 cases and 7 cases of bone cement leakage in groups A and B, respectively, which were asymptomatic para-vertebral or inter-vertebral leakage without intra-spinal leakage. Compared with the preoperative data, significant improvements in the VAS scores and ODI were observed at each follow-up interval. The VAS score and ODI in the A group were significantly lower than in the B group only within 2 months (P < 0.05). Compared with the preoperative data, the AH and KA in the 2 groups were improved (P < 0.05). There was no significant difference in AH and KA between the 2 groups at each follow-up interval (P > 0.05). LIMITATIONS: A single-center study. CONCLUSIONS: The unilateral PKP performed via the symptom-dominating side can effectively relieve back pain and improve the patient's quality of life at the early stage.

A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection.

Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and viral meningitis. Coxsackievirus infection may also play a role in the pathogenesis of acute myocardial infarction and in the increased risk of type 1 diabetes mellitus in adults. However, there are no approved vaccines or direct antiviral agents available to prevention or treatment of coxsackievirus infection. Here, we reported that GC376 potently inhibited CV-A10 infection in different cell lines without cytotoxicity, significantly suppressed production of viral proteins, and strongly reduced the yields of infectious progeny virions. Further study indicated that GC376, as viral 3C protease inhibitor, had the potential to restrain the cleavage of the viral polyprotein into individually functional proteins, thus suppressed the replication of CV-A10. Furthermore, the drug exhibited antiviral activity against coxsackieviruses of various serotypes including CV-A6, CV-A7 and CV-A16, suggesting that GC376 is a broad-spectrum anti-coxsackievirus inhibitor and the 3C protease is a promising target for developing anti-coxsackievirus agents.

Bimetallic polyphenol networks structure modified polyethersulfone membrane with hydrophilic and anti-fouling properties based on reverse thermally induced phase separation method.

In order to improve the hydrophobicity of traditional polyethersulfone (PES) membranes, this study combined the reverse thermally induced phase separation (RTIPS) method with the constructed bimetallic polyphenol networks (BMPNs) to prepare hydrophilic anti-fouling membranes. As for BMPNs, tannic acid (TA) was served as an intermediate to construct both the inner and surface hydrophilic layers of the PES membranes. On the one hand, etching Zeolitic imidazolate framework-8 (EZIF-8) with synergistic etching and surface functionalization via TA not only retained the high pore structure of MOFs, but also had good hydrophilicity. On the other hand, the MPN hydrophilic layer was formed on the membrane surface by the combination of TA from the surface of EZIF-8 and iron ions in the coagulation bath. Therefore, BMPNs structure penetrated the interior and surface of PES membrane, which greatly improved the hydrophilic properties. In addition, the membrane with porous surfaces and spongy cross sections by RTIPS method improved the permeability and mechanical properties of the membrane by several times compared with the membrane via NIPS method. The obtained membranes in this experiment showed excellent permeability, just like pure water flux reached 1662.16 L/m2 h, while BSA rejection rate remained at 92.78%. Compared with pure membrane, it showed a better flux recovery rate (FRR = 83.33%) after cleaning, and the reduction of irreversible (Rir = 16.67%) fouling indexes indicated that the adsorption of protein was inhibited. These results suggested that the hydrophilic anti-fouling PES membranes prepared by this method possessed great application potential in membrane separation technology.

Hydrophilic co-assembly of wheat gluten proteins and wheat bran cellulose improving the bioavailability of curcumin.

Low-cost wheat by-products have been modified to become an effective delivery system for curcumin. Wheat bran cellulose (WBC) and wheat gluten proteins (WPs) were co-assembled by a pH cycle and addition of sodium tripolyphosphate (STP). Fluorescence spectroscopy and zeta-potential evidenced that the embedding of WBC into the WPs favored the formation composites a relative unfolding state. Modifying the nanocomposite with STP lowered the Dh and PDI of the co-assembled structure. The nanocomplexes had a typical core-shell structure according to TEM characterization, where proteins aggregate to form a hydrophobic core and the hydrophilic WBC and STP crosslinked to form the shell. To improve the bioavailability of curcumin, it was encapsulated in WWBCs composites by participating in their structural co-assembly. In vitro simulated gastrointestinal digestion experiments showed that the curcumin encapsulated in WWBCs possessed gastrointestinal slow and controlled release function, with a final release of curcumin of 77.8 ± 2.3 %.

Can Additional Facet Joint Block Improve the Clinical Outcome of Kyphoplasty for Acute Osteoporotic Vertebral Compression Fractures?

BACKGROUND: Percutaneous kyphoplasty (PKP) has been reported to provide a favorable analgesic effect for pain caused by osteoporotic vertebral compression fractures (OVCFs). However, a systematic review demonstrated that pain relief was only reported for approximately 86% of kyphoplasty treatments. OBJECTIVES: To explore whether an additional facet joint block (FJB) can minimize pain and improve the clinical outcome of PKP in patients with acute OVCFs. STUDY DESIGN: Prospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: According to the inclusion and exclusion criteria, 194 patients were eventually included in our study; they were randomly divided into 2 groups of 97 patients each and treated with either PKP + FJB or PKP alone. Follow-up consultations were scheduled 1 day, 3 days, 1 week, 1 month, 3 months, and 1 year postoperatively; the demographic characteristics, related surgical information, and complications observed within both groups were recorded. The clinical evaluation parameters included the intraoperative satisfaction score, the Visual Analog Scale (VAS) score, and the Oswestry Disability Index (ODI). RESULTS: A total of 171 patients (61 men and 110 women; age range: 62-85 years) completed the full postoperative follow-up schedule, with 83 patients in the PKP + FJB group and 88 in the PKP group. No significant differences were observed in the genders, ages, preoperative bone mineral density, surgical levels, or volume of cement injected between the 2 groups (P > 0.05, respectively). The average duration of the surgeries in the PKP + FJB group was slightly longer than that in the PKP group (35.5 ± 4.8 min vs. 31.8 ± 4.3 min; P = 0.038), and in terms of the clinical outcomes, the average intraoperative satisfaction score was significantly higher in the PKP + FJB group (8.6 ± 1.1 vs. 6.3 ± 1.3; P < 0.001). Compared with the preoperative data, significant improvements in the VAS scores of back pain and ODI were observed at each follow-up interval (P < 0.05, respectively). These scores were significantly higher in the PKP + FJB group than in the PKP group; however, this was only observed within the first month after the procedure. LIMITATIONS: A single-center noncontrol study. CONCLUSIONS: The addition of an FJB (which in our study involved a unique combination of ropivacaine, prednisolone, and vitamin B12) improved the short-term clinical outcome of PKP for acute OVCFs. The local anti-inflammatory and analgesic effects on the facet joints resulted in higher intraoperative satisfaction and lower VAS and ODI scores for the first postoperative month when compared with the PKP group.

Cells on pores: a simulation-driven analysis of transcellular small molecule transport.

A biophysical, computational model of cell pharmacokinetics (1CellPK) is being developed to enable prediction of the intracellular accumulation and transcellular transport properties of small molecules using their calculated physicochemical properties as input. To test if 1CellPK can generate accurate, quantitative hypotheses and guide experimental analysis of the transcellular transport kinetics of small molecules, epithelial cells were grown on impermeable polyester membranes with cylindrical pores and chloroquine (CQ) was used as a transport probe. The effect of the number of pores and their diameter on transcellular transport of CQ was measured in apical-to-basolateral or basolateral-to-apical directions, at pH 7.4 and 6.5 in the donor compartment. Experimental and simulation results were consistent with a phospholipid bilayer-limited, passive diffusion transport mechanism. In experiments and 1CellPK simulations, intracellular CQ mass and the net rate of mass transport varied <2-fold although total pore area per cell varied >10-fold, so by normalizing the net rate of mass transport by the pore area available for transport, cell permeability on 3 mum pore diameter membranes was more than an order of magnitude less than on 0.4 mum pore diameter membranes. The results of simulations of transcellular transport were accurate for the first four hours of drug exposure, but those of CQ mass accumulation were accurate only for the first five minutes. Upon prolonged incubation, changes in cellular parameters such as lysosome pH rise, lysosome volume expansion, and nuclear shrinkage were associated with excess CQ accumulation. Based on the simulations, lysosome volume expansion alone can partly account for the measured, total intracellular CQ mass increase, while adding the intracellular binding of the protonated, ionized forms of CQ (as reflected in the measured partition coefficient of CQ in detergent-permeabilized cells at physiological pH) can further improve the intracellular CQ mass accumulation prediction.

Superparamagnetic iron oxide nanotheranostics for targeted cancer cell imaging and pH-dependent intracellular drug release.

Studies were conducted to develop antibody- and fluorescence-labeled superparamagnetic iron oxide nanoparticle (SPIO) nanotheranostics for magnetic resonance imaging (MRI) and fluorescence imaging of cancer cells and pH-dependent intracellular drug release. SPIO nanoparticles (10 nm) were coated with amphiphilic polymers and PEGylated. The antibody HuCC49ΔCH2 and fluorescent dye 5-FAM were conjugated to the PEG of iron oxide nanoparticles (IONPs). Anticancer drugs doxorubicin (Dox), azido-doxorubicin (Adox), MI-219, and 17-DMAG containing primary amine, azide, secondary amine, and tertiary amine, respectively, were encapsulated into IONPs. The encapsulation efficiency and drug release at various pHs were determined using LC-MS/MS. The cancer targeting and imaging were monitored using MRI and fluorescent microscopy in a colon cancer cell line (LS174T). The pH-dependent drug release, intracellular distribution, and cytotoxicity were evaluated using microscopy and MTS assay. The PEGylation of SPIO and conjugation with antibody and 5-FAM increased SPIO size from 18 to 44 nm. Fluorescent imaging, magnetic resonance imaging (MRI) and Prussian blue staining demonstrated that HuCC49ΔCH2-SPIO increased cancer cell targeting. HuCC49ΔCH2-SPIO nanotheranostics decreased the T(2) values in MRI of LS174T cells from 117.3 ± 1.8 ms to 55.5 ± 2.6 ms. The loading capacities of Dox, Adox, MI-219, and 17-DMAG were 3.16 ± 0.77%, 6.04 ± 0.61%, 2.22 ± 0.42%, and 0.09 ± 0.07%, respectively. Dox, MI-219 and 17-DMAG showed pH-dependent release while Adox did not. Fluorescent imaging demonstrated the accumulation of HuCC49ΔCH2-SPIO nanotheranostics in endosomes/lysosomes. The encapsulated Dox was released in acidic lysosomes and diffused into cytosol and nuclei. In contrast, the encapsulated Adox only showed limited release in endosomes/lysosomes. HuCC49ΔCH2-SPIO nanotheranostics target-delivered more Dox to LS174T cells than nonspecific IgG-SPIO and resulted in a lower IC(50) (1.44 µM vs 0.44 µM). The developed HuCC49ΔCH2-SPIO nanotheranostics provides an integrated platform for cancer cell imaging, targeted anticancer drug delivery and pH-dependently drug release.

[Polymethylmethacrylate-augmented screw fixation in treatment of senile thoracolumbar tuberculosis combined with severe osteoporosis].

OBJECTIVE: To explore the safety and effectiveness of polymethylmethacrylate-augmented screw fixation (PASF) in the treatment of elderly thoracolumbar tuberculosis combined with severe osteoporosis. METHODS: The clinical data of 20 elderly patients with thoracolumbar tuberculosis and severe osteoporosis who underwent PASF after anterior or posterior debridement and bone grafting and met the selection criteria between December 2012 and December 2014 were retrospectively analyzed. There were 8 males and 12 females with an average age of 68.5 years (range, 65-72 years). T value of bone mineral density was -4.2 to -3.6, with an average of -3.9. There were 12 cases of thoracic tuberculosis, 3 cases of thoracolumbar tuberculosis, and 5 cases of lumbar tuberculosis. The diseased segments involved T 3-L 4, including 11 cases of single-segment disease, 6 cases of double-segment disease, and 3 cases of multi-segment disease. The disease duration was 3-9 months, with an average of 6 months. The preoperative spinal nerve function of the patients was evaluated by the American Spinal Injury Association (ASIA) grading. There were 2 cases of grade A, 5 cases of grade B, 6 cases of grade C, 4 cases of grade D, and 3 cases of grade E. Postoperative imaging examination was used to evaluate the bone graft fusion and paravertebral abscess absorption, and to measure the Cobb angle of the segment to evaluate the improvement of kyphosis. The levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were tested. The visual analogue scale (VAS) score, Oswestry disability index (ODI), and ASIA grading were used to evaluate the effectivreness before operation, at 1 month after operation, and at last follow-up. The clinical cure of tuberculosis was also evaluated. RESULTS: All operation successfully completed. The operation time was 154-250 minutes, with an average of 202 minutes; the intraoperative blood loss was 368-656 mL, with an average of 512 mL. All 20 patients were followed up 18-42 months, with an average of 26.8 months. The postoperative pain and symptoms of tuberculosis in all patients relieved, and the paravertebral abscess was absorbed, reaching the cure standard for spinal tuberculosis. All bone grafts fusion achieved within 1 year after operation. Only 1 case had asymptomatic bone cement leakage into the paravertebral veins, and the remaining patients had no serious complications such as bone cement leakage in the spinal canal, pulmonary embolism, and neurovascular injury. At last follow-up, spinal cord nerve function significantly improved when compared with preoperative one. Among them, ASIA grading were 7 cases of grade C, 8 cases of grade D, and 5 cases of grade E, showing significant difference when compared with preoperative one ( Z=2.139, P=0.000). VAS score, ODI score, segmental Cobb angle, ESR, and CRP at 1 month after operation and at last follow-up were significantly improved when compared with preoperative ones ( P<0.05); there was no significant difference between 1 month after operation and last follow-up ( P>0.05). During the follow-up, no complications such as failure of internal fixation, proximal junctional kyphosis, or tuberculosis recurrence occurred. CONCLUSION: For elderly patients with thoracolumbar tuberculosis and severe osteoporosis, PASF treatment is safe and effective.

Nature-inspired antimicrobial polymers--assessment of their potential for biomedical applications.

We explored the potential of poly(oxonorbornene)-based synthetic mimics of antimicrobial peptides (SMAMPs), a promising new class of antimicrobial polymers with cell-selectivity and low resistance development potential, for clinical applications. We evaluated their antimicrobial activity against a panel of seven clinical and regulatory relevant bacteria strains, and tested their toxicity with two different kinds of primary human cells. For the antimicrobial activity, we performed the minimum inhibitory concentration (MIC) assay and determined the minimum bactericidal concentration (MBC) according to the NCCLS guidelines. The results revealed specific problems that may occur when testing the antimicrobial activity of amphiphilic cationic polymers, and confirmed the working hypothesis that the more hydrophilic SMAMP polymers in our portfolio were 'doubly selective', i.e. they are not only selective for bacteria over mammalian cells, but also for Gram-positive over Gram-negative bacteria. The data also showed that we could improve the broad-band activity of one SMAMP, and in combination with the results from the cell toxicity experiments, identified this polymer as a promising candidate for further in-vitro and in-vivo testing. Transmission electron studies revealed that the cellular envelopes of both E. coli and S. aureus were severely damaged due to SMAMP action on the bacterial membrane, which strengthened the argument that SMAMPs closely resemble antimicrobial peptides. To test cell toxicity, we used the traditional hemolysis assay with human red blood cells, and the novel xCelligence assay with primary human fibroblasts. The data reported here is the first example in which a hemolysis assay is benchmarked against the xCelligence assay. It revealed that the same trends were obtained using these complementary methods. This establishes the xCelligence assay with primary human cells as a useful tool for SMAMP characterization.

[Effects of sulfur- and polymer-coated controlled release urea fertilizers on wheat yield and quality and fertilizer nitrogen use efficiency].

A field experiment was conducted to study the effects of sulfur- and polymer-coated controlled release urea fertilizers on wheat yield and its quality, plow layer soil inorganic nitrogen (N) contents, and fertilizer N use efficiency. Compared with traditional urea fertilizer, both sulfur- and polymer-coated controlled release urea fertilizers increased the grain yield by 10.4%-16.5%, and the grain protein and starch contents by 5.8%-18.9% and 0.3%-1.4%, respectively. The controlled release urea fertilizers could maintain the topsoil inorganic N contents to meet the N requirement for the wheat, especially during its late growth stage. In the meantime, the fertilizer N use efficiency was improved by 58.2%-101.2%. Polymer-coated urea produced better wheat yield and higher fertilizer N use efficiency, compared with sulfur-coated controlled release urea.

Physicochemical characterization and biocompatibility in vitro of biphasic calcium phosphate/polyvinyl alcohol scaffolds prepared by freeze-drying method for bone tissue engineering applications.

In this study, a well developed porous biphasic calcium phosphate (BCP)/polyvinyl alcohol (PVA) scaffold was prepared by emulsion foam freeze-drying method possessed moderate inter-connected pores and porosity. The SEM analysis showed that BCP nano-particles could disperse uniformly in the scaffolds, and the pore size, porosity, and compressive strength could be controlled by the weight ratio of BCP/PVA. The in vitro degradation and cytocompatibility of scaffolds were examined in this study. The degradation analysis showed the prepared scaffolds have a low variation of pH values (approximately 7.18-7.36) in SBF solution, and have the biodegradation rate of BCP/PVA scaffolds decreased with the increase of PVA concentration. Moreover, MTT assay indicated that the BCP/PVA porous scaffold has no negative effects on cells growth and proliferation, and the hBMSCs possessed a favorable spreading morphology on the BCP/PVA scaffold surface. The inter-connected pore structure, mechanical strength, biodegradation rate and cytocompatibility of the prepared BCP/PVA scaffold can meet essential requirements for blame bearing bone tissue engineering and regeneration.

Structure, corrosion behavior and mechanical property of a novel poly(vinyl alcohol) composite in simulated body fluid.

The data for long-term drug-delivery systems are scarce compared to the short-term systems because the required research efforts are more time-consuming. In this study, we report a novel cross-linked composite based on poly(vinyl alcohol) (PVA) containing cupric ions for long-term delivery, which is helpful for contraception and trace element balance in the human body. The composition, corrosion products, crystal structure, chemical structure and mechanical stability of the composite, after being immersed in simulated body fluid (SBF) for one year, were studied by X-ray fluorescence spectroscopy (XRF), X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and mechanical testing. The results show that no other new elements, such as P, Cl and Ca, appear on the surface of the composite and no Cu(2)O was formed after immersion in SBF for one year. The effectiveness of copper can be greatly improved and the side-effects caused by these compounds might also be eliminated. Furthermore, this novel composite exhibits long-term mechanical stability in SBF. The present in vitro long-term data suggest that this novel copper-containing composite may serve as a substitute for conventional materials of copper-containing intrauterine devices (Cu-IUDs) and as a carrier for controlled-release material in a variety of other applications.