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Background: Central line (CL)-associated bloodstream infection (CLABSI) poses a major threat to patient safety and is associated with additional cost. This study investigated the sustained effect of multimodal interventions focusing on CL bundle improvement in the adult intensive care units (ICUs) of a teaching hospital in Taiwan., Methods: A before-after prospective study was conducted in 17 adult ICUs of a medical center in northern Taiwan from January 2009 to December 2013. Many interventions that aimed to facilitate CL bundle implementation were initiated in January 2011. The incidence rates of CLABSI and catheter-related bloodstream infection (CRBSI) were compared between the baseline and intervention periods. Catheter utilization ratios and microbiological characteristics were also analyzed., Results: The incidence rates of both CLABSI and CRBSI decreased significantly from the baseline to the intervention periods (from 9.27 to 7.66 per 1000 CL-days and from 1.51 to 0.89 per 1000 CL-days, respectively). The yearly incidence rate decreased by up to 31% (incidence rate ratio [IRR], 0.69; 95% confidence interval [CI], 0.59-0.81) for CLABSI and 59% (IRR, 0.41; 95% CI, 0.26-0.65) for CRBSI since the initiation of the interventions. The catheter utilization ratio also decreased from 0.71 to 0.63 (p < 0.001). Microbiological analysis showed that among all CLABSI isolates, the proportion of coagulase-negative staphylococci significantly decreased during the intervention period., Conclusion: Implementing multimodal interventions focusing on CL bundle improvement was effective in reducing the incidence rates of CLABSI and CRBSI in Taiwan's adult ICUs., (Copyright © 2017. Published by Elsevier B.V.)

As a regulator of osteogenesis, microRNA-218 (miR-218) is reported to promote osteogenesis of mesenchymal stem cells (MSCs). However, the in vivo osteogenic effect of miR-218 remains elusive. In this study, miR-218 was confirmed to promote osteogenic differentiation of MSCs by stimulating the alkaline phosphatase activity, calcium nodule formation, and osteogenic marker gene expression. For in vivo study, the miR-218-overexpressing BMSCs were locally administrated into the fracture sites in a femur fracture mouse model. Based on the X-rays, micro-computed tomography, mechanical testing, histology, and immunohistochemistry examinations, miR-218 overexpression improved new bone formation and accelerated fracture healing. These findings suggest that miR-218 may be a promising therapeutic target for bone repair in future clinical applications.

Rationale: Spinal cord infarction is rarely caused by hypercoagulable states. Polycythemia vera (PV) is a myeloproliferative neoplasm that can contribute to thrombotic events due to increased blood viscosity. We report a case of spinal cord infarction due to extensive aortic thrombosis caused by PV., Patient Concerns: A 56-year-old man presented with acute paraplegia and urinary retention during heavy physical exertion., Diagnoses: Imaging studies revealed spinal cord infarction at the T9 to T12 levels and aortoiliac occlusive disease. PV was diagnosed during workup for elevated hemoglobin level INTERVENTIONS:: The patient received intravenous hydration and anticoagulation for spinal cord infarction. PV was managed with phlebotomy and hydroxyurea. Courses of inpatient and outpatient rehabilitation programs were also given., Outcomes: The patient became urinary catheter-free 5 months after disease onset, and was able to walk with walker. The American Spinal Injury Association Impairment scale also improved from C at diagnosis to D during last follow-up., Lessons: Etiologic workup is important for patients with spinal cord infarction to direct specific treatment strategies. Physical exertion may act as a trigger for infarction in patients at risk for thrombotic events, and monitoring of neurologic status during and after periods of exercise is warranted.

Rationale: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disease. Progressive motor symptoms such as dystonia and spasticity begin in childhood and relentlessly become incapacitating later in life. Treatments including anticholinergics and iron chelation are usually ineffective. Botulinum toxin type A (BoNT-A) is effective for adult patients with dystonia or spasticity., Patient Concerns: We reported a 10-year-old female patient with advanced PKAN, manifesting as generalized dystonia and spasticity., Diagnosis: The patient was diagnosed with PKAN by a pediatric neurologist., Interventions: The patient received BoNT-A injection., Outcomes: The effect was obvious at four weeks after the injection, with an improvement of 25% in Barry-Albright Dystonia Scale and 4% in Functional Independence Measure for Children score. Furthermore, there was a 3.8% reduction in Parenting Stress Index Short Form score and 8.3% improvement in Pain and Impact of Disability domain in the score of Cerebral Palsy Quality of Life for Children., Lessons: BoNT-A injection was effective to improve functional independence and to alleviate stress of caregivers in the patient with advanced PKAN.

The nuclear shell structure, which originates in the nearly independent motion of nucleons in an average potential, provides an important guide for our understanding of nuclear structure and the underlying nuclear forces. Its most remarkable fingerprint is the existence of the so-called magic numbers of protons and neutrons associated with extra stability. Although the introduction of a phenomenological spin-orbit (SO) coupling force in 1949 helped in explaining the magic numbers, its origins are still open questions. Here, we present experimental evidence for the smallest SO-originated magic number (subshell closure) at the proton number six in 13-20 C obtained from systematic analysis of point-proton distribution radii, electromagnetic transition rates and atomic masses of light nuclei. Performing ab initio calculations on 14,15 C, we show that the observed proton distribution radii and subshell closure can be explained by the state-of-the-art nuclear theory with chiral nucleon-nucleon and three-nucleon forces, which are rooted in the quantum chromodynamics.

Background: To evaluated the experiences of double balloon enteroscopy (DBE) for obscure gastrointestinal bleeding., Methods: From October 2003 to November 2009, a total of 124 patients with obscure gastrointestinal bleeding were investigated using DBE. A total of 142 procedures (84 per oral and 58 per rectal route) were performed by the same endoscopist., Results: The average insertion time was 71.4 (20-199) minutes per-orally; the average insertion time was 139.2 min for the first 5 procedures, 109.4 min for 6-10 procedures, 76.6 min for 11-15, 66.4 min for 16-20, 67.4 min for 21-25, 59 min for 26-30, 66 min for 31-35, 52 min for 36-40, 42.9 min for 41-45, 44.6 min for 46-50, 42.2 min for 51-55, 38.6 min for 56-60, 44.6 min for 61-65, 37.8 min for 66-70, 38.8 min for 71-75, 44.3 min for 76-80, and 36.6 min for 61-84 procedures; there was no statistical difference after the first ten procedures. The average insertion time was 92.1 (22-260) minutes per-rectally; the average insertion time was 159.6 min for the first 5 procedures, 98.4 min for 6-10 procedures, 86.6 min for 11-15, 76.4 min for 16-20, 82.4 min for 21-25, 75.0 min for 26-30, 78.2 min for 31-35, 72.4 min for 36-40, 68.2 min for 41-45, 66.9 min for 45-50, and 71.4 min for 51-58 procedures; there was no statistical difference after the first five procedures. For the different genders these was no statistically significant difference. There were no differences regarding the diagnostic yield between the previous factors. The overall diagnostic yield was 82.4%., Conclusion: DBE is a safe and effective means of diagnosing and managing patients with obscure gastrointestinal bleeding. However, because of its time-consuming, DBE has a learning curve to overcome before a physician can become an expert to achieve adequate insertion times with good diagnostic and therapeutic rates., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

The spinal cord injury (SCI) is a detrimental neurological disease involving the primary mechanical injury and secondary inflammatory damage. Curtailing the detrimental neuroinflammation would be beneficial for spinal cord function recovery. Microglia reside in the spinal cord and actively participate in the onset, progression and perhaps resolution of post-SCI neuroinflammation. In the current study, we tested the effects of methylene blue on microglia both in vitro and in a rat SCI model. We found that methylene blue inhibited the protein levels of IL-1β and IL-18 rather than their mRNA levels in activated microglia. Further investigation indicated that methylene blue deceased the activation of NLRP3 inflammasome and NLRC4 inflammasome in microglia in vitro . Moreover, in the rat SCI model, the similar effect of methylene blue on post-SCI microglia was also observed, except that the activation of NLRC4 inflammasome was not seen. The inhibition of microglia NLRP3 inflammasome was associated with down-regulation of intracellular reactive oxygen species (ROS). The administration of methylene blue mitigated the overall post-SCI neuroinflammation, demonstrated by decreased pro-inflammatory cytokine production and leukocyte infiltrates. Consequently, the neuronal apoptosis was partially inhibited and the hind limb locomotor function was ameliorated by methylene blue treatment. Our research highlights the role of methylene blue in inhibiting post-SCI neuroinflammation, and suggests that methylene blue might be used for SCI therapy.

Drug-resistant Klebsiella pneumoniae, especially extended-spectrum β-lactamase (ESBL)- and/or AmpC β-lactamase-producing strains, is an emerging problem worldwide. However, few data focusing on drug susceptibility of K. pneumoniae from community is available. In this study, we analyzed 1016 K. pneumoniae isolates from outpatients or those visiting emergency rooms collected during 2002-2012 from Taiwan Surveillance of Antimicrobial Resistance program. Significantly decreased susceptibilities to 3 rd generation cephalosporins and ciprofloxacin were found during the study period. By 2012, susceptibility to cefotaxime and ciprofloxacin was 83.6% and 81.6%, respectively. The prevalence of ESBL-producers increased from 4.8% in 2002 to 11.9% in 2012 (P = 0.012), while that of AmpC β-lactamase-producers increased from 0% to 9.5% in the same period (P < 0.001). Phylogenic analysis of the ESBL and AmpC-β-lactamase-producers by pulsed-field gel electrophoresis and multi-locus sequence typing revealed wide genetic diversity even among the most common sequence type 11 isolates (33.0%). By multivariate analysis, later study year, elderly, and urine isolates were associated with carriage of ESBL genes, while only urine isolates were associated with carriage of AmpC β-lactamase genes. Further studies are needed to determine which antibiotics are reasonable empirical therapy options for patients presenting with severe sepsis that might be caused by K. pneumoniae.

Study Design: We introduced an adenoviral vector expressing interleukin-1β (IL-1β) small-hairpin RNA (shRNA) into the injured spinal cords to evaluate the therapeutic potential of IL-1β downregulation in a rat model of spinal cord injury (SCI)., Objectives: The purpose of this study was to investigate the possible protective effects of the IL-1β downregulation on traumatic SCI in rats., Setting: Department of Orthopedic Surgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, People's Republic of China., Methods: An adenoviral shRNA targeting IL-1β was constructed and injected at the T12 section 7 days before SCI. The rats' motor functions were evaluated by the Basso-Beattie-Bresnahan (BBB) rating scale. Immunofluorescence, enzyme-linked immunosorbent assay, flow-cytometric analysis and western blots were also performed., Results: Animals downregulating IL-1β had significantly better recovery of locomotor function and less neuronal loss after SCI. In addition, IL-1β downregulation significantly decreased tumor necrosis factor-alpha (TNF-α) level and Bax expression, reduced the activity of caspase-3 and increased Bcl-2 expression after SCI., Conclusion: This study demonstrated that the IL-1β downregulation may have potential therapeutic benefits for both reducing secondary damages and improving the outcomes after traumatic SCI.

Dibutyl phthalate (DBP) is used worldwide in solvents and plasticizers. The cytotoxicity and potential tumorigenic effect of DBP have been reported. DBP has also been shown to impact reproductive function. In this study, to further evaluate the effects of DBP on granulosa cells (GCs), we treated rat GCs in vitro with DBP before evaluation of the biological alterations of these GCs. We found that DBP did not induce significant GC death at the tested concentrations. However, follicle-stimulating hormone (FSH)-induced KIT ligand (KITLG) expression in GCs was significantly reduced at both mRNA and protein levels by DBP treatment in a dose-dependent manner. The down-regulation of KITLG was due to the down-regulation of expression of FSH receptor (FSHR) in GCs. Down-regulation of FSHR impaired FSH-induced intracellular signaling in GCs, demonstrated by decreased phosphorylation of AKT and mechanistic target of rapamycin (mTOR). Furthermore, DBP treatment also reduced FSH-induced expression of hypoxia-inducible factor 1-alpha (HIF1A), which is an important signaling component for KITLG expression. Other FSH-induced biological effects, such as production of estradiol and progesterone, as well as GC proliferation, were also suppressed by DBP. Therefore, our study discovered a unique mechanism underlying the toxicity of DBP on GCs. These findings may initiate the development of novel therapeutic interventions for DBP-induced damage to GCs., (© 2016 by the Society for the Study of Reproduction, Inc.)

Heart rate is an important clinical measure that is often used in pathological diagnosis and prognosis. Valid detection of irregular heartbeats is crucial in the clinical practice. We propose an artificial neural network using the calculated pulse rate to detect irregular interbeats. The proposed system measures the calculated pulse rate to determine an "irregular interbeat on" or "irregular interbeat off" event. If an irregular interbeat is detected, the proposed system produces a danger warning, which is helpful for clinicians. If a non-irregular interbeat is detected, the proposed system displays the calculated pulse rate. We include a flow chart of the proposed software. In an experiment, we measure the calculated pulse rates and achieve an error percentage of < 3% in 20 participants with a wide age range. When we use the calculated pulse rates to detect irregular interbeats, we find such irregular interbeats in eight participants.

Background: Understanding the mechanisms underlying neuronal death in spinal cord injury (SCI) and developing novel therapeutic approaches for SCI-induced damage are critical for functional recovery. Here we investigated the role of heme oxygenase-1 (HO-1) in neuroprotection after SCI., Methods: Adeno-associated virus expressing HO-1 was prepared and injected into rat spinal cords before SCI model was performed. HO-1 expression, inflammasome activation, and the presence of inflammatory cytokines were determined by quantitative polymerase chain reaction, immunohistological staining, immunoblot, and immunoprecipitation. Neuronal apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling. The hindlimb locomotor function was evaluated for extent of neurologic damage. In an in vitro model, hydrogen peroxide was used to induce similar inflammasome activation in cultured primary spinal cord neurons, followed by evaluation of above parameters with or without transduction of HO-1-expressing adeno-associated virus., Results: Endogenous HO-1 expression was found in spinal cord neurons after SCI in vivo, in association with the expression of Nod-like receptor protein 1 (NLRP1) and the formation of NLRP1 inflammasomes. Administration of HO-1-expressing adeno-associated virus effectively decreased expression of NLRP1, therefore alleviating NLRP1 inflammasome-induced neuronal death and improving functional recovery. In the in vitro model, exogenous HO-1 expression protected neurons from hydrogen peroxide-induced neuronal death by inhibiting NLRP1 expression. In addition, HO-1 inhibited expression of activating transcription factor 4 (ATF4), which is a transcription factor regulating NLRP1 expression., Conclusions: HO-1 protects spinal cord neurons after SCI through inhibiting NLRP1 inflammasome formation.

The skin transcriptome of Bufu bufo gargarizans was determined by conventional methods. A novel full length cDNA coding for a Cathelicidin precursor was identified by transcriptomic data assembling, annotation and blast search of corresponding data banks. According to the known processing methods of Cathelicidin family members, present reported novel Cathelicidin precursor of B. bufo gargarizans might be cleaved at 2 possible sites of the same precursor and generate both BG-CATH25 and BG-CATH29 as mature molecules. The deduced BG-CATH25 and BG-CATH29 were synthesized with purity>95% to evaluate the properties and bactericidal activities. The secondary structural characteristics of both BG-CATH25 and BG-CATH29 in different solutions were determined by Circular Dichroism (CD) Analysis. CD results indicated that random coil conformation were the main structural elements for both BG-CATH25 and BG-CATH29 in different buffer systems. Antimicrobial activities against tested bacterial strains were carried out by plating method. Both BG-CATH25 and BG-CATH29 showed strong antibacterial activities against Aeromonas hydrophila, with MIC values of 1.25, 10 mg•L⁻¹, respectively. However, both of them showed weak bactericidal activities against human pathogenic bacteria, like Escherichia coli (ATCC25922）,Staphylococcus aureus (ATCC25923）and Pseudomonas aeruginosa (ATCC 27853)., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To examine the effectiveness of overnight orthokeratology lenses made with Boston XO2, highly gas-permeable lens material for the temporary correction of myopia., Methods: Myopic individuals from 9 to 62 years of age were eligible. Participants ≤ 12 years of age were required to have myopia ≤-4.00 D and astigmatism ≤ 1.50 D, and for those 13-62 years of age myopia ≤-5.00 D and astigmatism ≤ 3.00 D. All participants were required to have normal healthy eyes and not be receiving any ocular medications or systemic medications likely to affect the results of visual acuity. Participants wore the lenses for a minimum of 7h during sleep, and were evaluated on day 1 and weeks 1, 2, 4, 12, and 24. Success was defined as LogMAR ≤ 0.1., Results: A total of 126 participants (63.5% females) with a mean age of 20.4 ± 11.5 years were recruited. Baseline LogMAR, and vertical and horizontal corneal curvature were 0.8, 7.7 mm, and 7.9 mm, respectively, in both eyes. A consistent decrease in LogMAR was noted from day 1 to week 12. The success rate increased with length of time (from 33.9% to 100% for the right eye and from 35.5% to 100% for the left eye from day 1 to week 24). No severe complications were noted., Conclusion: Overnight orthokeratology with lenses made of Boston XO2 material are effective and safe for the temporary reduction of myopia., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The frequent use of antibacterial agents and the exposure of the patients to lifesaving intervention processes are consistently associated with the increased chance of nosocomial infections and the emergence of multidrug resistant microorganisms in the hospital environment. Thus, new antimicrobial agents are of unmet need to treat the severe nosocomial infections caused by these putative pathogens resistant to currently available agents., Method: Design, synthesis, and biological evaluation of analogues of nitazoxanide (NTZ), an FDA approved thiazolide antiparasitic, as new antimicrobial agents against nosocomial pathogens were described. The NTZ analogues were rationally explored on the basis of either increasing the electronic resonance effects at the nitrothiazolide moiety or improving the anionic form of the whole NTZ structure., Results: The MICs and MBCs values of these NTZ analogues against prevalent nosocomial pathogens were measured. The benzologous analogues 3a and 4a and p-chlorobenzenesulfonamides 8d and 9d exhibited tremendous antimicrobial activities, which were 100- to 2000-fold more potent than NTZ and ciprofloxacin., Conclusion: The results demonstrated that delicate manipulation of the NTZ core structure could lead to promising antimicrobial agents against the nosocomial pathogens.

We demonstrate a simple and unique double-Brillouin-frequency spaced multiwavelength structure. It uses the reflection property of an isolator and fiber loop mirror which is made of a 50:50 coupler. This scheme has only one loop, instead of two or more loops, to separate the odd and even Stokes waves generated by Brillouin scattering. The light going into loop cavity can be absorbed twice to produce a Brillouin Stokes wave twice in one round loop, so a double-Brillouin-frequency spaced multiwavelength harmonics wave can be achieved in the output of the structure. Finally, our experiment successfully achieves a double-Brillouin-frequency space of about 0.1475 and 0.1734 nm in two different type structures.

Protein glutathionylation is an important protein post-translational modification associated with oxidative stress, in which the thiol groups of cysteine residues react with glutathione and form disulfide bonds. Glutathionylation has been shown to affect protein structure and modulate protein function, and is implicated in the regulation of signaling and metabolic pathways. Glutathionylation of human hemoglobin has been known for decades. However, only glutathionylation on Cys-93 of β-globin has been characterized. In this study, we used nanoflow liquid chromatography-nanospray ionization multistage mass spectrometry (nanoLC-NSI/MS(n)) under a data-dependent scan mode to identify sites of glutathionylation in human hemoglobin by accurate mass measurement and by their MS(2) and MS(3) spectra. After human hemoglobin was incubated with oxidized glutathione, alkylated and trypsin digested, all three cysteine residues, i.e., α-Cys-104, β-Cys-93, and β-Cys-112, were found to be glutathionylated. Glutathionylation at these sites was also detected in hemoglobin freshly isolated from human blood samples by the consecutive reaction monitoring at the MS(3) scan stage, and the extent of modification of each site was quantified relative to the alkylated parent peptide in the selected reaction monitoring (SRM) chromatograms. The peak area ratio of glutathionylated and alkylated parent peptides under MS(3) and MS(2)-SRM, respectively, represents the relative extent of glutathionylation. The extents of glutathionylation at α-Cys-104 and β-Cys-93 in hemoglobin of 20 smokers were significantly higher than those in 20 nonsmokers with a p value of 0.0008 and <0.0001, respectively. Moreover, there are statistically significant correlations between the extent of glutathionylation at α-Cys-104 and β-Cys-93 and the number of cigarettes smoked per day as well as smoking index. This assay is highly specific and sensitive as it requires as little as 2 μg of hemoglobin isolated from one drop of blood. These results suggest that this assay might be feasible in measuring the extent of glutathionylation in hemoglobin as a low-invasive biomarker of oxidative stress. To our knowledge, this is the first report identifying all three cysteine residues being glutathionylated in human hemoglobin and quantifying the extent of glutathionylation at the peptide level using multistage mass spectrometry.

The current study was performed to evaluate the mechanisms and therapeutic effects of overexpressing neuroglobin (Ngb) on spinal cord injury (SCI). Adeno-associated virus (AAV) was injected in the T12 section 7 days before SCI. Animals were randomly divided into four groups: a sham group, a vehicle group, an AAV-EGFP group and an AAV-Ngb group. Recovery of hind limb locomotor function was determined during the 3-week post operation period by the Basso, Beattie and Bresnahan locomotor rating scale. At 24 h after SCI and at the end of the study, the segments of spinal cord, centered with the lesion site were harvested for histopathological analysis. Immunofluorescence was performed using antibodies to recognize neuN in the lesion sections. At 24 h after SCI, the spinal cord tissue samples were removed to analyze tissue concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA). Apoptotic cells were assessed using a terminal deoxynucleotidyl transferase, dUTP nick end labeling (TUNEL) kit. The expression of bcl-2, bax, cytochrome c, and cleaved caspase-3, were determined by Western blot assay and immunostaining analysis. The results showed that animals overexpressing Ngb had significantly greater recovery of locomotor function, less neuronal loss and fewer apoptotic cells. In addition, overexpressing Ngb significantly increased bcl-2 expression and SOD level, decreased bax expression, attenuated the release of cytochrome c from mitochondria to the cytosol fraction, and reduced the activity of caspase-3 and MDA level after SCI. These findings suggest, that overexpressing Ngb can significantly improve the recovery of locomotor function. This neuroprotective effect may be associated with the inhibition of neural apoptosis via the mitochondrial pathway., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Acanthopanax trifoliatus (L) Merr (AT) is commonly used as an herbal medicine and edible plant in some areas of China and other Asian countries. AT is thought to have anticancer effects, but potential mechanisms remain unknown. To assess the anticancer properties of AT, we exposed prostate cancer cells to AT extracts and assessed cell proliferation and signaling pathways. An ethanol extract of AT was suspended in water followed by sequential extraction with petroleum ether, ethyl acetate and n-butanol. PC-3 cells were treated with different concentrations of each extract and cell viability was determined by the MTT and trypan blue exclusion assays. The ethyl acetate extract of the ethanol extract had a stronger inhibitory effect on growth and a stronger stimulatory effect on apoptosis than any of the other extracts. Mechanistic studies demonstrated that the ethyl acetate extract suppressed the transcriptional activity of NF-kB, increased the level of caspase-3, and decreased the levels of phospho-Erk1/2 and phospho-Akt. This is the first report on the anticancer activity of AT in cultured human prostate cancer cells. The results suggest that AT can provide a plant-based medicine for the treatment or prevention of prostate cancer.

Due to the advantages of good scalability, flexibility, low cost, ease of processing, 3D-stacking capability, and large capacity for data storage, polymer-based resistive memories have been a promising alternative or supplementary devices to conventional inorganic semiconductor-based memory technology, and attracted significant scientific interest as a new and promising research field. In this review, we first introduced the general characteristics of the device structures and fabrication, memory effects, switching mechanisms, and effects of electrodes on memory properties associated with polymer-based resistive memory devices. Subsequently, the research progress concerning the use of single polymers or polymer composites as active materials for resistive memory devices has been summarized and discussed. In particular, we consider a rational approach to their design and discuss how to realize the excellent memory devices and understand the memory mechanisms. Finally, the current challenges and several possible future research directions in this field have also been discussed., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: This study aimed to investigate whether or not hypoxia-inducible factor-1α (HIF-1α) gene variants are associated with the susceptibility and clinical characteristics of lumbar disc degeneration (LDD)., Methods: We examined 320 patients with LDD and 447 gender- and age-matched control subjects. We also determined the HIF-1α gene variants, including C1772T (P582S) and G1790A (A588T) polymorphisms., Results: Significant differences were observed in allelic and genotypic distributions of 1790 A > G polymorphisms between LDD cases and control subjects. Logistic regression revealed that 1790 AA genotypes indicated a protective effect against the development of LDD. The HIF-1α 1790 A > G polymorphisms also affected the severity of LDD as evaluated based on the modified Japanese Orthopedic Association (mJOA) scores. The 1790 AA genotype carriers exhibited significantly lower mJOA scores than AG and GG carriers. C1772T did not show any association with the risk and severity of LDD., Conclusion: Our study suggested that HIF-1α 1790 A > G polymorphisms may be used as a molecular marker to determine the susceptibility and severity of LDD.

Fluoroquinolones have been a class of important synthetic antimicrobial agents broadly and effectively used in clinic for infectious diseases. In this study, the synthesis of a range of fluoroquinolone derivatives with 4-(carbopiperazin-1-yl)piperazinyl moieties at the C7 position and their inhibition of bacterial pathogens commonly disseminated in hospital environment were described. The results indicated that a 7-[4-(4-(benzoyl)carbopiperazin-1-yl)]piperazinyl derivative 5h and two 7-[4-(4- (benzenesulfonyl)carbopiperazin-1-yl)]piperazinyl derivatives 5k and 5l showed more promising growth inhibition of ciprofloxacin-resistant P. aeruginosa (CRPA) with MIC values as low as 16 μg/mL which is 16-fold more potent than ciprofloxacin, while most of other derivatives maintained potency against methicillin-resistant Staphylococcus aureus (MRSA).

Objective: This study aims to investigate the potentially protective effect of neuroglobin (Ngb) gene-modified bone marrow mesenchymal stem cells (BMSCs) on traumatic spinal cord injury (SCI) in rabbits., Methods: A lentiviral vector containing an Ngb gene was constructed and used to deliver Ngb to BMSCs. Ngb gene-modified BMSCs were then injected at the SCI sites 24 hours after SCI. The motor functions of the rabbits were evaluated by the Basso-Beattie-Bresnahan rating scale. Fluorescence microscopy, quantitative real-time PCRs, Western blots, malondialdehyde (MDA) tests, and terminal deoxynucleotidyltransferase-mediated UTP end labeling assays were also performed., Results: Ngb expression in the Ngb-BMSC group increased significantly. A more significant functional improvement was observed in the Ngb-BMSC group compared with those in the other groups. Traumatic SCI seemingly led to an increase in MDA level and number of apoptotic cells, which can be prevented by Ngb-BMSC treatment., Conclusion: This study demonstrates that Ngb gene-modified BMSCs can strengthen the therapeutic benefits of BMSCs in reducing secondary damage and improving the neurological outcome after traumatic SCI. Therefore, the combined strategy of BMSC transplantation and Ngb gene therapy can be used to treat traumatic SCI.

Objective: This study aimed to evaluate the outcomes in patients undergoing balloon-assisted enteroscopy (BAE) with heat probe or argon plasma coagulation and to identify risk factors for recurrent bleeding., Methods: Data of the patients who were consecutively referred to our institution with angiodysplastic bleeding of the small intestine between August 2005 and February 2010 were reviewed. These 39 patients underwent BAE and were followed up for 6 months., Results: In all, 31 patients had melena and 8 had hematochezia. On BAE, 26 patients received endoscopic therapy, 3 underwent surgical intervention due to endoscopic therapy failure, and 10 underwent observation because a definite source of bleeding was not identified. Ten patients (25.6%) had recurrent bleeding during follow-up, including eight patients in the endoscopic therapy group and two in the observation group. Higher rates of recurrent bleeding were observed in association with the presence of melena initially (P = 0.028), but there were no significant differences in the rate of recurrence between patients who did and did not receive endoscopic therapy (P = 0.470). Age greater than 65 years (P = 0.058) and jejunal bleeding (P = 0.050) tended to increase the risk of recurrent bleeding compared with other factors., Conclusions: BAE may be a beneficial approach to treat angiodysplastic bleeding in the small intestine. Elderly patients and those with melena or jejunal bleeding should be closely monitored for recurrent bleeding., (© 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background: As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro., Methods: To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting., Results: We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect., Conclusions: From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications.

The mTOR pathway is a central control of cell growth, proliferation, metabolism, and survival, and is deregulated in most cancers. Cancer cells are addicted to increased activity of mTOR kinase-mediated signaling pathways, leading to numerous inhibitors of mTOR signaling in preclinic and clinical trials for cancer therapy. Phosphorus-containing sirolimus (FIM-A), which targets mTOR signaling, inhibits cancer cell growth in vitro. Here we report that FIM-A reduces the angiogenesis and proliferation of osteosarcoma both in vitro and in vivo. In cultured osteosarcoma cell lines, FIM-A inhibited cell proliferation and arrested cells in the G1 phase of the cell cycle, accompanied with reduction of VEGF and HIF-1alpha. With in vivo mouse osteosarcoma xenografts, FIM-A treatment resulted in the inhibition of mTORC1 signaling as demonstrated by the decreased phosphorylation of p70S6K1 and 4E-BP1. Consistent with this finding, FIM-A significantly decreased the average tumor volume, nuclei staining of PCNA, and the number of intratumoral microvessels. Our data demonstrated that targeting mTORC1 by FIM-A inhibited the growth of osteosarcoma in vitro and in vivo, providing the basis for further development of FIM-A as a therapy for osteosarcoma patients.

Background/purpose: Quadriceps-sparing minimally invasive total knee arthroplasty (TKA) has been proposed to limit surgical dissection without compromising surgical outcome. We conducted a prospective and randomized study to compare the outcomes of patients who underwent quadriceps-sparing TKA with the outcomes of those who underwent standard medial parapatellar TKA, after a 2-year follow-up period., Methods: Eighty primary TKA procedures that were to be performed in 60 osteoarthritis patients were randomly assigned to either a quadriceps-sparing (40 knees) or a standard medial parapatellar (40 knees) group. All surgeries were designed to set the prosthesis with a femoral component alignment of 7° valgus and a tibial component alignment that was perpendicular to the tibial shaft. Surgical time and tourniquet time were recorded. Outcome variables included knee function, as defined by a hospital for special surgery knee score; quadriceps muscle strength, which was measured by an isokinetic dynamometer; pain, as indicated on a visual analog scale; prosthetic position, which was measured on plain radiograph; and range of motion., Results: Patients who underwent the 38 quadriceps-sparing and 37 standard TKA procedures completed the 2-year follow-up period without any infection or revision. The mean surgical time and tourniquet time were significantly longer in the quadriceps-sparing group. The mean peak quadriceps muscle strength, hamstring muscle strength, normalized muscle balance (hamstring/quadriceps ratio), pain score, function score, and range of motion were comparable in both groups at 2 months and 2 years. In the quadriceps-sparing group, both the femoral and the tibial components were significantly more varus-deviated from the expected position., Conclusions: Patients undergoing quadriceps-sparing and standard medial parapatellar TKA had comparable outcomes for quadriceps muscle strength, hamstring-quadriceps balance, and knee function; however, the quadriceps-sparing TKA was more time consuming surgically and resulted in a less accurate prosthesis position., (Copyright © 2012. Published by Elsevier B.V.)

A ternary polymer memory device based on a single polymer with on-chain Ir(III) complexes is fabricated by combining multiple memory mechanisms into one system. Excellent ternary memory performances-low reading, writing, and erasing voltages and good stability for all three states-are achieved., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To verify the clinical efficacy on rear thigh muscles strain of athletes treated with surrounding needling of electroacupuncture and hot compress of Chinese medicine., Methods: Eighty-six cases were randomly divided into an observation group and a control group, 43 cases in each one. In the observation group, surrounding needling of electroacupuncture and hot compress of Chinese medicine were used at Ashi points around the local affected area of rear thigh muscles. In the control group, conventional needling method and local cupping were applied at Chengfu (BL 36), Yinmen (BL 37), Weizhong (BL 40), etc. The treatment was given once a day. Ten treatments made one session. Two sessions were required. The score of rear thigh muscles pain, swelling and tenderness, walking function recovery and the total score were compared before and after treatment between two groups. The efficacy was compared between two groups., Results: The score of pain, swelling and tenderness, walking function recovery and the total score were reduced obviously after treatmeat in two groups (all P < 0.01), and the improvements in the observation group were superior to those in the control group (P < 0.01, P < 0.05). The cured and remarkably effective rate was 83.7% (36/43) in the observation group, which was better than 60.5% (26/43) in the control group (P < 0.05)., Conclusion: The efficacy of the surrounding needling of electroacupuncture and the hot compress of Chinese medicine is significant on rear thigh muscles strain for the athletes, which is superior to that of the conventional needling method and cupping in terms of the improvements in the symptoms and physical signs as well as the recovery of the walking function.

Study Design: We introduced a lentiviral vector containing the neuroglobin (Ngb) gene into the injured spinal cords to evaluate the therapeutic potential of Ngb in a rabbit model of spinal cord injury (SCI)., Objectives: It is not clear whether Ngb has the neuroprotective role to SCI. The purpose of this study was to investigate the possible protective effects of the Ngb overexpression on traumatic SCI in rabbits., Setting: Department of Orthopedic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, People's Republic of China., Methods: A lentiviral vector containing Ngb gene was constructed and injected at the SCI sites 24 h after SCI. The rabbits' motor functions were evaluated by the Basso-Beattie-Bresnahan rating scale. Quantitative real-time PCRs, western blots, malondialdehyde (MDA) tests and terminal deoxynucleotidyl transferase-mediated UTP end labeling assays were also performed., Results: The Ngb expression in the LV-Ngb group increased significantly at days 7, 14 and 21. A more significant functional improvement was observed in the LV-Ngb group compared with the improvements in all other groups at days 14 and 21. The traumatic SCI seemed to lead to an increase in the levels of MDA and in the number of the apoptotic cells, which could be prevented by the LV-Ngb treatment., Conclusion: This study demonstrated that the Ngb overexpression may have potential therapeutic benefits for both reducing secondary damages and improving the outcomes after traumatic SCI.

Studies showed that levels of ethylated DNA adducts in certain tissues and urine are higher in smokers than in nonsmokers. Because cigarette smoking is a major risk factor of various cancers, DNA ethylation might play an important role in cigarette smoke-induced cancer formation. Among the ethylated DNA adducts, O(2)-ethylthymidine (O(2)-edT) and O(4)-ethylthymidine (O(4)-edT) are poorly repaired and are accumulated in the body. In addition, O(4)-edT possesses promutagenic properties. In this study, we have developed a highly sensitive, accurate, and quantitative assay for simultaneous detection and quantification of O(2)-edT, N(3)-edT (N(3)-ethylthymidine), and O(4)-edT adducts by isotope dilution nanoflow liquid chromatography-nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS). Under the highly selected reaction monitoring (H-SRM) mode, the detection limit of O(2)-edT, N(3)-edT, and O(4)-edT injected on-column was 5.0, 10, and 10 fg, respectively. The quantification limit for the entire assay was 50, 100, and 100 fg of O(2)-edT, N(3)-edT, and O(4)-edT, respectively, corresponding to 1.1, 2.3, and 2.3 adducts in 10(9) normal nucleotides, respectively, starting with 50 μg of DNA (from 1.5-2.0 mL of blood). Levels of O(2)-edT, N(3)-edT, and O(4)-edT in 20 smokers' leukocyte DNA were 44.8 ± 52.0, 41.1 ± 43.8, 48.3 ± 53.9 in 10(8) normal nucleotides, while those in 20 nonsmokers were 0.19 ± 0.87, 4.1 ± 13.3, and 1.0 ± 2.9, respectively. Levels of O(2)-edT, N(3)-edT, and O(4)-edT in human leukocyte DNA are all significantly higher in smokers than in nonsmokers, with pvalues of 0.0004, 0.0009, and 0.0004, respectively. Furthermore, levels of O(2)-edT show a statistically significant association (γ = 0.4789, p = 0.0327) with the smoking index in smokers. In the 40 leukocyte DNA samples, the extremely significant statistical correlations (p < 0.0001) are observed between levels of O(2)-edT and O(4)-edT (γ = 0.9896), between levels of O(2)-edT and N(3)-edT (γ = 0.9840), and between levels of N(3)-edT and O(4)-edT (γ = 0.9901). To our knowledge, this is the first mass spectrometry-based assay for ethylated thymidine adducts. Using this assay, the three ethylated thymidine adducts were detected and quantified for the first time. Therefore, this highly sensitive, specific, and accurate assay should be clinically feasible for simultaneous quantification of the three ethylated thymidine adducts as potential biomarkers for exposure to ethylating agents and for cancer risk assessment.

Background and Aim: The technical performance of colonoscopy performed in deeply sedated patients differs from that performed without sedation or under minimal to moderate sedation. The aim of this study is to evaluate the factors affecting cecal intubation during colonoscopy performed under deep sedation., Methods: A total of 5352 consecutive subjects who underwent a screening colonoscopy as part of a health check-up between January 2008 and December 2008 at an academic hospital were reviewed. All endoscopies were performed with deep sedation using combination propofol or propofol alone. Data collected included characteristics of the patients (age, gender, body mass index, bowel habits, history of abdominal or pelvic surgery, quality of bowel preparation, and presence/absence of colonic diverticula) and characteristics of the colonoscopists (experience level, colonoscopy procedure volume, and instrument handling method). These factors were analyzed to evaluate their impact on cecal intubation rates., Results: The crude cecal intubation rate was 98% and the adjusted cecal intubation rate was 98.3%. The mean cecal intubation time was 5.6 ± 3.2 min. Multivariate logistic regression analysis demonstrated that patient age greater than 60 years, constipation, poor colon preparation and a two-person colonoscopy procedure were independently associated with lower cecal intubation rates., Conclusions: Colonoscopy performed under deep sedation by experienced colonoscopists results in high cecal intubation rates. Among the significant patient-related predictors influencing the cecal intubation, the quality of the bowel preparation was the only modifiable factor. When performed by experienced hands, the one-person method was associated with higher cecal intubation rates than the two-person method., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are at an increased risk of peritonitis following colonoscopy with or without polypectomy. Guidelines for peritoneal dialysis patients recommend administration of prophylactic antibiotics and drainage of the abdomen before colonoscopy. In this report, we describe a 53-year-old woman on CAPD who underwent colonoscopy with polypectomy and developed peritonitis within 24 hours. She presented with severe abdominal pain, typical rebounding tenderness, and turbid dialysate containing increased white blood cells with a predominance of neutrophils. A culture of the patient's peritoneal fluid grew polymicrobial species including Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. She was treated with intraperitoneal and intravenous administration of combination antibiotics, and she fully recovered within 3 weeks. We suggest that nephrologists and endoscopists should be familiar with the risks and follow the guidelines to prevent such complications in CAPD patients. If peritonitis occurs, medical therapy with antibiotics should be considered before surgical intervention for catheter salvage.

Exocyclic DNA adducts, including 1,N(2)-propano-2'-deoxyguanosine derived from acrolein (AdG) and crotonaldehyde (CdG) and the three lipid peroxidation-related etheno adducts 1,N(6)-etheno-2'-deoxyadenosine (εdAdo), 3,N(4)-etheno-2'-deoxycytidine (εdCyt), and 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-εdGuo), play an important role in cancer formation and they are associated with oxidative-stress-induced DNA damage. Saliva is an easily accessible and available biological fluid and a potential target of noninvasive biomarkers. In this study, a highly sensitive and specific assay based on isotope dilution nanoflow LC-nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS) is developed for simultaneous detection and quantification of these five adducts in human salivary DNA. The levels of AdG, CdG, εdAdo, εdCyd, and 1,N(2)-εdGuo, measured in 27 human salivary DNA samples from healthy volunteers, were determined as 104 ± 50, 7.6 ± 12, 99 ± 50, 72 ± 49, 391 ± 198 (mean ± SD) in 10(8) normal nucleotides, respectively, starting with 25 μg of DNA isolated from an average of 3 mL of saliva. Statistically significant correlations were found between levels of εdAdo and εdCyd (γ = 0.8007, p < 0.0001), between levels of εdAdo and 1,N(2)-εdGuo (γ = 0.6778, p = 0.0001), between levels of εdCyd and 1,N(2)-εdGuo (γ = 0.5643, p = 0.0022), between levels of AdG and 1,N(2)-εdGuo (γ = 0.5756, p = 0.0017), and between levels of AdG and εdAdo (γ = 0.3969, p = 0.0404). Only 5 μg of DNA sample was analyzed for simultaneous quantification of these adducts. The easy accessibility and availability of saliva and the requirement for the small amount of DNA samples make this nanoLC-NSI/MS/MS assay clinically feasible in assessing the possibility of measuring 1,N(2)-propano-2'-deoxyguanosine and etheno adducts levels in human salivary DNA as noninvasive biomarkers for DNA damage resulting from oxidative stress and for evaluating their roles in cancer formation and prevention.

Background: Our study was designed to (1) investigate the risk factors associated with cervical or trochanteric hip fractures; and (2) identify the risk factors for increased mortality in the elderly population sustaining hip fractures, after adjusting the miscellaneous baseline prefracture conditions., Methods: Two hundred seventeen elder patients with first-time, low-trauma hip fractures were enrolled. The follow-up time ranged from 35 months to 56 months. Potential risk factors for hip fracture types included (1) the 77 items on the self-reported questionnaire; (2) the body height, weight, and body mass index; (3) tests of coordination, handgrip strength, and peak expiratory flow rate; and (4) the bone mineral density variables. GTFN ratio was defined as the bone mineral density ratio between the greater trochanter and the femoral neck. Multivariate logistic regression and Cox regression models were used for analysis. The population attributable risk proportion of death to each significant factor was estimated., Results: Risk factors for trochanteric fractures include a GTFN ratio ≤0.81, being male, and an age >80 years. Risk factors for higher mortality after hip fracture included trochanteric fracture, body mass index ≤20 (kg/m), poor self-assessed health status, peak expiratory flow rate ≤215 (L/min), being male, illiteracy, and coordination abnormality, in the declining order of population attributable risk proportion. Trochanteric fractures had a significantly higher cumulative mortality at 36 months, 48 months, and 60 months than cervical fractures., Conclusions: The novel GTFN ratio was associated with hip fracture sites. Clinically, cervical and trochanteric fractures represent different disease entities because of the difference in their mortality rates.

Aim: To assess the long-term outcome of endoscopic hemorrhoid ligation (EHL) for the treatment of symptomatic internal hemorrhoids., Methods: A total of 759 consecutive patients (415 males and 344 females) were enrolled. Clinical presentations were rectal bleeding (593 patients) and mucosal prolapse (166 patients). All patients received EHL at outpatient clinics. Hemorrhoid severity was classified by Goligher's grading. The mean follow-up period was 55.4 mo (range, 45-92 mo)., Results: The number of band ligations averaged 2.35 in the first session for bleeding and 2.69 for prolapsed patients. Bleeding was controlled in 587 (98.0%) patients, while prolapse was reduced in 137 (82.5%) patients. After treatment, 93 patients experienced anal pain and 48 patients had mild bleeding. Patient subjective satisfaction was 93.6%. Repeat treatment or surgery was performed if symptoms were not relieved in the first session. In the bleeding group, the recurrence rate was 3.7% (22 patients) at 1 year, and 6.6% and 13.0% at 2 and 5 years. In the prolapsed group, the recurrence rate was 3.0%, 9.6% and 16.9% at 1, 2 and 5 years, respectively., Conclusion: EHL is an easy and well-tolerated procedure for the treatment of symptomatic internal hemorrhoids, with good long-term results.

Background: Peutz-Jeghers syndrome (PJS) is a very rare disease that often causes severe complications such as bowel obstruction or gastrointestinal tract bleeding. In the past, it was usually treated by using surgical intervention despite the associated complications. Balloon-assisted enteroscopy (BAE) has been documented as an effective and safe method for the diagnosis and treatment of small bowel lesions. Hence, we conducted this study to verify whether BAE is useful for patients with PJS., Aim: To evaluate the safety and efficacy of BAE with prophylactic polypectomy in patients with PJS., Methods and Patients: From August 2005 to February 2010, 6 consecutive patients were diagnosed with PJS after pathological and clinical examination, and underwent BAE examination and polypectomy at Chang Gung Memorial Hospital, an academic tertiary referral center., Results: Six consecutive patients (4 men and 2 women) diagnosed with PJS underwent BAE with polypectomy. BAE was performed 17 times for complete examination of the entire small bowel. The range of the diameter of the removed polyps was 1-6 cm. No immediate complications such as hemorrhage or hollow organ perforation were noted during the procedure, and no patient developed intussusception during the follow-up period (32 ± 17.5 months)., Conclusion: BAE with polypectomy is useful for patients with PJS in order to reduce the complications of the condition.

We investigated a possible association between interleukin (IL)-10 single nucleotide polymorphisms (SNPs) and susceptibility to and severity of lumbar disc degeneration (LDD) in a Chinese cohort of 320 patients with LDD and 269 gender- and age-matched controls. The degree of disc degeneration was determined by magnetic resonance imaging using Schneiderman's classification. Genetic analysis of IL-10 promoter polymorphisms (at -1082 A/G, -819 T/C, and -592 A/C) was carried out by PCR-RFLP. A total of 134 herniated lumbar intervertebral discs were collected during surgery for IL-10 mRNA detection. For SNPs at -592, the A allele and AA genotype frequencies were significantly higher in LDD patients than in controls. Similarly, the AA genotype and A allele frequencies at -1082 were significantly higher in cases than in controls. Among the LDD subjects, carriers of AA at -592 and GG at -1082 had significantly lower mean IL-10 mRNA expression than the other two genotypes. The SNPs at each locus were not significantly associated with severity grade in the LDD patients. Logistic regression analyses showed that the AA at -1082, AA at -592, and IL-10 mRNA expression level were independent risk factors for LDD. We conclude that the IL-10 SNPs at -1082 A/G and -592 A/C as well as IL-10 mRNA in the herniated lumbar intervertebral discs are associated with susceptibility to LDD in this Chinese cohort, but not with disease severity.

Aim: To evaluate the efficacy of endoscopic diagnosis and therapy for jejunal diverticular bleeding., Methods: From January 2004 to September 2009, 154 patients underwent double-balloon enteroscopy (DBE) for obscure gastrointestinal bleeding. Ten consecutive patients with jejunal diverticula (5 males and 5 females) at the age of 68.7 ± 2.1 years (range 19- 95 years) at Chang Gung Memorial Hospital, Academic Tertiary Referral Center, were enrolled in this study., Results: Of the 10 patients, 5 had melena, 2 had hematochezia, 2 had both melena and hematochezia, 1 had anemia and dizziness. DBE revealed ulcers with stigmata of recent hemorrhage in 6 patients treated by injection of epinephrine diluted at 1:10 000, Dieulafoy-like lesions in 4 patients treated by deploying hemoclips on the vessels, colonic diverticula in 2 patients, and duodenal diverticula in 3 patients, respectively. Of the 2 patients who underwent surgical intervention, 1 had a large diverticulum and was referred by the surgeon for DBE, 1 received endoscopic therapy but failed due to massive bleeding. One patient had a second DBE for recurrent hemorrhage 7 mo later, which was successfully treated with a repeat endoscopy. The mean follow-up time of patients was 14.7 ± 7.8 mo., Conclusion: DBE is a safe and effective treatment modality for jejunal diverticular bleeding.

The spectral features of ground objects are not only the brief contents of mechanism of remote sensing, but also the important basis in remote sensing application. As one of main components of terrestrial ecosystems, urban forest plays a key role in maintaining urban ecosystem balance. In the present paper, the authors adopted FieldSpec 3 portable spectroscope made by American ASD Company, and investigated or examined some spots in the Kangjian park of Shanghai, China. The spectra of euonymus japonicus L. cv, hypericum monogynum, sabina chinensis, ophiopogon japonicus, viburnum awabuki, and buxus sinica were measured. According to the actual conditions, the authors analyzed the data noise characteristic of the spectrum and got rid of the noise with Savitzky Golay method. Meanwhile, differential spectrum technology was used to remove the environmental background influence. Then the authors analyzed their features and variation of these spectral curves from the vegetation canopy and leaf level respectively. The research on spectral reflectance characteristics for urban vegetations is very significant. And the result of this research can be used for the study of physical chemistry performances of urban vegetation, remote sensing retrieval, vegetation classification, vegetation survey and environmental monitoring in urban area.

Amphotericin B (AmB) is an antifungal antibiotic the activity of which has been associated with modulation of pro-inflammatory cytokines expression in cultured cells. Herein we reveal that co-administration with AmB enhances the immunogenicity of oral Lip-JENS1 vaccine which derived from liposomes functionalized with DSPC (distearoylphosphatidylcholine) and cholesterol (2:1, molar ratio)-bearing JE virus NS1 protein (600 microg ml(-1)). Oral single dose of Lip-JENS1 elicited a detectable serum NS1-specific IgG antibody response from a mouse model. Remarkably, the addition of AmB (125 microg per mouse), particularly, 2 h prior to, but not simultaneously with, the administration of Lip-JENS1 significantly enhanced the systemic antigen-specific antibody response, providing superior protection against lethal JEV challenges. Further, we observed AmB-induced the transcription of cytokine expression and translocation of transcriptional factor NF-kappaB from the cytoplasm to the nucleus for the murine macrophage J774A.1. Moreover, Peyer's-patch lymphocytes (PPL) from AmB-treated mice produced high levels of IL-1beta, IL-6 and TNF-alpha expression compared to the corresponding control of cells from non-treated mice. Taken together, the results suggest that AmB exerts a profound influence upon mucosal vaccination with Lip-JENS1, possibly playing an adjuvant-augmented role to "fine-tune" humoral as well as cellular immune response, thus conferring enhanced protective immunity for immunising individuals against JE infection., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Taping has been used to treat patellofemoral pain syndrome for more than 20 years, but its effectiveness is still controversial., Purpose: This study was undertaken to investigate the effect and predictors of effectiveness of taping in the treatment of patellofemoral pain syndrome., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 118 consecutive patients with patellofemoral pain syndrome were recruited; 100 of them completed this study. Patient sex, age, body mass index, Q angle, lateral patellar displacement, and lateral patellofemoral angle were recorded/measured. One therapist applied adhesive tape to each patient by the McConnell method. Patients scored their pain level on a 100-mm visual analog scale during stepping down from an 8-in platform, before and after taping. The change of score was evaluated by paired t test. Patients with a visual analog scale score decrease of 20 mm or more after taping were considered responsive, and the others were considered nonresponsive. The influences of the aforementioned factors, plus pretaping visual analog scale score, on the effectiveness of taping were analyzed by multivariate logistic regression., Results: The overall mean visual analog scale score decreased significantly after taping (from 49.0 to 29.3 mm; P < .001). There were 66 patients in the responsive group and 34 in nonresponsive group. Among the factors, body mass index, lateral patellofemoral angle, and Q angle were significant predictors of effectiveness. The responsive group had significantly smaller mean lateral patellofemoral angle, larger mean Q angle, and larger mean pretaping visual analog scale score than the nonresponsive group., Conclusion: Taping was an effective treatment for patellofemoral pain syndrome, but was less effective in patients with higher body mass index, larger lateral patellofemoral angle, and smaller Q angle.

Background: Difficulty with the proximal lesion approach and durability of endoscopic ultrasonography (EUS) instruments usually limits its application for lower gaotrointestina (GI) lesions to locoregional staging of rectal cancer. This study investigated the value of colonoscopic miniprobe ultrasonography for differential diagnosis and treatment strategy in patients with colorectal subepithelial lesions (SEL)., Methods: Miniprobe ultrasonography was Performed in 40 consecutive patients with suspected colorectal SEL or residual lesions after endoscopic resection at one medical center by the same endoscopist (C-J Lin). The EUS images and procedure records were reviewed. The final diagnosis of these lesions was confirmed by cross section imaging, histopathologic findings, or clinical follow-up., Results: Miniprobe EUS allowed high-resolution imaging and a successful approach to all colorectal SEL through the working channel of a sigmoidoscope or colonoscope without breakdown of the miniprobe. Thirteen patients, suspected of having rectal carcinoid tumors (mean size, 6.9 +/- 3.3 mm), were treated radically by endoscopic mucosal resection using a transparent cap (EMRC) after EUS confirmation of no muscular invasion. Three patients had no residual or recurrent carcinoid tumor on EUS examination after previous empiric polypectomy or biopsy. EUS detected submucosal lipomas (mean size, 18.5 mm; range, 8.6-25.6 mm) in ten patients however, only two patients underwent endoscopic resection. Five patients had suspected rectal myogenic stromal tumors on EUS; three were transferred for surgical resection due to uterine myoma compression (N = 2) or mucinous adenocarcinoma of the appendix with rectal metastasis (N = 1), and two had uterine myoma detected by gynecologic ultrasound or CT. One appendiceal stone with orifice obstruction mimicking cecal submucosal tumor was proved by surgical resection. One patient had hemorrhoids proved by hemorrhoidectomy. One patient was proved to have proctitis cystica profunda by EMRC. The other six patients had various benign lesions, which were diagnosed and followed-up by EUS without progression. In thirty-five of forty patients (88%) colorectal SEL were managed uneventfully according to EUS interpretation., Conclusions: Miniprobe ultrasonography can be a useful supplement to routine colonoscopy and provide treatment guidance for suspected colorectal subepithelial lesions.

microRNAs (miRNAs) are endogenous non-coding RNAs that spatiotemporally modulate mRNAs in a post-transcriptional manner. The engineering of viruses by insertion of a tissue-specific miRNA recognition element (MRE) into viral mRNA can restrict viral tissue tropism. In this study we employed dengue virus (DEN) replicons to investigate whether miRNAs are able to suppress flavivirus replication through the targeting of non-polyadenylated viral mRNA. Because liver infection by DEN may contribute to the virus pathogenesis, we inserted an MRE of hepatic-specific microRNA-122 (miR-122) into its 3'-untranslated region (3'-UTR) to test the feasibility of creating a liver-restricted DEN replicon. Our results demonstrate that incorporation of the miR-122-MRE confers upon the DEN replicon an inhibitory susceptibility to miR-122 targeting, suggesting that DEN can be engineered to exert the desired replication restriction effect to avoid infection of vital tissues/organs. This approach provides an additional layer of biosafety and thus has great potential for use in the rational development of safer flavivirus vaccines., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Etheno DNA adducts are promutagenic DNA lesions derived from exogenous industrial chemicals, as well as endogenous sources including lipid peroxidation. Furthermore, levels of etheno adducts in tissue DNA are elevated in cancer-prone tissues. In this study, we have developed a highly sensitive and specific stable isotope dilution nanoflow LC-nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS) assay for simultaneous detection and accurate quantification of 1,N(6)-etheno-2'-deoxyadenosine (epsilondAdo), 3,N(4)-etheno-2'-deoxycytidine (epsilondCyt), and 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-epsilondGuo) in tissue DNA. Typically, [(13)C(1),(15)N(2)]epsilondAdo, [(15)N(3])epsilondCyd, and [(13)C(1),(15)N(2)]1,N(2)-epsilondGuo were added to calf thymus, human placenta, or human leukocyte DNA as internal standards, and the mixture was subjected to enzyme hydrolysis to form the nucleosides. The etheno adducts in DNA hydrolysate were enriched by a reversed phase solid-phase extraction column before analysis by nanoLC-NSI/MS/MS under the highly selective reaction monitoring (H-SRM) mode. This nanoLC-NSI/MS/MS assay achieved attomole-level sensitivity with the detection limit of 0.73, 160, and 34 amol for the respective standard epsilondAdo, epsilondCyd, and 1,N(2)-epsilondGuo injected on-column, while the quantification limit for the entire assay was 0.18, 4.0, and 3.4 fmol, respectively. The levels of epsilondAdo, epsilondCyd, and 1,N(2)-epsilondGuo in human placental DNA were 28.2, 44.1, and 8.5 adducts in 10(8) normal nucleosides, respectively. The levels of epsilondAdo, epsilondCyd, and 1,N(2)-epsilondGuo in 11 human leukocyte DNA samples were 16.2 +/- 5.2, 11.1 +/- 5.8, and 8.6 +/- 9.1 (mean +/- S.D.) in 10(8) normal nucleotides, respectively, starting from 30 mug of DNA or 1-1.5 mL of blood, and all the relative standard deviations were within 10%. An aliquot equivalent to 6 mug of DNA hydrolysate was used for analysis by this nanoLC-NSI/MS/MS. Thus, this highly sensitive and specific nanoLC-NSI/MS/MS method is suitable for accurate quantification of the three lipid peroxidation-derived etheno DNA adducts as noninvasive biomarkers in clinical studies for cancer risk assessment and for evaluation of preventive agents.

Unlabelled: In this prospective study, we compared outcomes after repair of humeral nonunions when morsellized fresh-frozen allograft or autograft was used to augment repair by intramedullary nailing. Sixty-five patients with humeral shaft nonunions of greater than 6 months' duration and gross instability at the nonunion site were included and treated by locked nailing, interfragmentary wiring, and bone grafting. Graft type was determined by patient preference. Outcomes assessed included union rate and functional recovery of the arm. Secondary end points included operative blood loss, operation time, hospital stay, time to fracture healing, and complications. Twenty-eight patients with autografts and 36 with allografts were followed up more than 2 years. The baseline conditions of the two groups were similar. The autograft group had greater blood loss and longer operative time than the allograft group. The autograft group also had a longer hospital stay. The healing rate, time to healing, and functional scores did not differ between these two groups. In the autograft group, 43% reported pain and limited mobility as a result of the donor site. We concluded that when used in association with locked nailing for humeral nonunions, allografts can achieve treatment results similar to autografts but without donor site complications., Level of Evidence: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Humans are exposed to acrolein and crotonaldehyde due to environmental pollution and endogenous lipid peroxidation. These aldehydes react with the 2'-deoxyguanosine moiety of DNA, forming the exocyclic 1,N2-propano-2'-deoxyguanosine adducts AdG and CdG. These adducts are mutagenic lesions, and they play an important role in cancer and neurodegenerative diseases. In this study, a highly sensitive and quantitative assay was developed for simultaneous detection and quantification of AdG and CdG isomers in human placenta and leukocyte DNA by isotope dilution nanoflow LC with nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS). The on-column detection limits (S/N > or = 3) of AdG and CdG were 15 and 8.9 amol, respectively. The quantification limits of AdG and CdG for the entire assay were 619 and 297 amol, respectively, corresponding to 9.8 and 4.7 adducts in 10(9) normal nucleotides, respectively, starting with 20 microg of DNA. Different enzyme hydrolysis methods were compared, and the optimal hydrolysis conditions were employed for the assay. Levels of AdG and CdG in human placental DNA (20 microg) were 108 and 26 in 10(8) normal nucleotides, respectively, with the respective relative standard deviation (RSD) of 2.6% and 3.1% (n = 3). Levels of AdG and CdG in 9 human leukocyte DNA samples were 78 +/- 23 (mean +/- SD) and 6.2 +/- 3.8 (mean +/- SD) in 10(8) normal nucleotides, respectively, starting from 30 microg of DNA. Using this assay, only 4-6 microg of DNA sample was subjected to this nanoLC-NSI/MS/MS system for analysis. Only 1-1.5 mL of blood is needed for measuring AdG and CdG levels in leukocyte DNA. Thus, it is clinically feasible using this highly sensitive assay to investigate the potential of using these adducts as noninvasive biomarkers for DNA damage resulting from acrolein and crotonaldehyde and to study their roles in cancer development and prevention.

Our study was conducted to compare radiographic alignments and functional outcomes with 2 approaches to minimal-incision total knee arthroplasty (TKA): the minimal-incision medial parapatellar (MP) approach and the quadriceps-sparing (QS) approach with side-cutting instruments. Sixty patients (80 knees) with primary osteoarthritis were randomly assigned to receive MP or QS TKA. Postoperative alignment of the femoral component was significantly less valgus, and postoperative alignment of the tibial component was significantly more varus with the QS approach than with the MP approach. One tibial outlier and 3 femoral outliers were observed with QS TKA. The overall postoperative hip-knee-ankle axis was more varus, and surgical time was longer with QS TKA. Short-term isokinetic peak muscle torque, postoperative pain, and functional outcomes did not differ between the approaches.

Double-balloon enteroscopy (DBE) is an effective tool for diagnosing and treating obscure gastrointestinal bleeding. The aim is to describe how outcomes differ with patient setting (with DBE diagnosis and intervention, with DBE diagnosis but without intervention, and without DBE diagnosis), and thus demonstrate the value of endoscopic intervention when encountering potential bleeder during DBE. From November 2003 to January 2008, 90 patients with obscure gastrointestinal bleeding presented with DBE at our tertiary referral center. A total of 113 DBE procedures were carried out. Overall diagnostic yield was 75.6% (68/90). Endoscopic intervention was performed in 58 (85.3%) of the 68 patients with potential bleeder. The 90 patients were divided into three settings: with endoscopic diagnosis and intervention (n = 58), with endoscopic diagnosis but without intervention (n = 10), and without endoscopic diagnosis (n = 22). Rebleeding rates for the three groups were 22.4%, 60%, and 22.7%, respectively. For the 35 patients diagnosed with vascular lesions, the rebleeding rates in patients with and without endoscopic intervention, were 38.5% (10/26) and 66.7% (6/9), respectively. One (0.9%) severe adverse event occurred during the 113 procedures, and the patient died. DBE is an effective tool for diagnosing and treating obscure gastrointestinal bleeding. DBE involves relatively safe procedures and has an acceptable complication rate. When potential bleeders are encountered during the procedure, especially for vascular lesions, therapeutic intervention should be attempted, since the intervention-related complication rate is acceptable, and such intervention can reduce the rebleeding rate and enhance the cost-effectiveness of DBE.