Search

Xiao-Tian Zhang,* Zhen-Yang Mao,* Xiang-Yun Jin, Yu-Gang Wang, Yu-Qi Dong, Chao Zhang Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao Zhang; Yu-Qi Dong, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Pudong New Area, Shanghai, People’s Republic of China, Tel +86-13817307997 ; +86-13331873590, Email drzhangchao@sina.coml; dyqrjgk@126.comPurpose: Delayed skin healing in diabetic wounds is a major clinical problem. The tRNA-derived small RNAs (tsRNAs) were reported to be associated with diabetes. However, the role of tsRNAs in diabetic wound healing is unclear. Our study was designed to explore the tsRNA expression profile and mine key potential tsRNAs and their mechanism in diabetic wounds.Methods: Skin tissues of patients with diabetic foot ulcers and healthy controls were subjected to small RNA sequencing. The role of candidate tsRNA was explored by loss- and gain-of-function experiments in HUVECs.Results: A total of 55 differentially expressed tsRNAs were identified, including 12 upregulated and 43 downregulated in the diabetes group compared with the control group. These tsRNAs were mainly concentrated in intercellular interactions and neural function regulation in GO terms and enriched in MAPK, insulin, FoxO, calcium, Ras, ErbB, Wnt, T cell receptor, and cGMP-PKG signaling pathways. tRF-Gly-CCC-039 expression was upregulated in vivo and in vitro in the diabetic model. High glucose disturbed endothelial function in HUVECs, and tRF-Gly-CCC-039 mimics further harmed HUVECs function, characterized by the suppression of proliferation, migration, tube formation, and the expression of Coll1a1, Coll4a2, and MMP9. Conversely, the tRF-Gly-CCC-039 inhibitor could attenuate high-glucose-induced endothelial injury to HUVECs.Conclusion: We investigated the tsRNAs expression profile in diabetic foot ulcers and defined the impairment role of tRF-Gly-CCC-039 in endothelial function in HUVECs. This study may provide novel insights into accelerating diabetic skin wound healing.Keywords: diabetic foot ulcers, skin healing, tsRNA expression profile, tRF-28-Q1Q89P9L84DF, endothelial damage

Bo Wang,1,* Peng Li,1,* Lei Shangguan,2,* Jun Ma,3,* Kezheng Mao,4 Quan Zhang,5 Yiguo Wang,6 Zhongyang Liu,1,2 Keya Mao1 1Department of Orthopedics, Chinese PLA General Hospital, Beijing, 100853, China; 2Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710032, China; 3Department of Orthopedics Trauma Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China; 4Department of Orthopedics, Orthopedics Hospital of Zhengzhou City, Zhengzhou, Henan, 450052, China; 5Department of Orthopedics, People’s Hospital of Tianjin City, Tianjin, 300121, China; 6Department of Orthopedics, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, China *These authors contributed equally to this work Introduction: Failed back surgery syndrome is a situation where there is failure after lumbar surgery aimed at correcting lumbar disease that is characterized by continuous back and/or leg pain. Epidural fibrosis and adhesions are among the major causes of failed back surgery syndrome. In recent years, several biomaterials have been applied as barriers or deterrents to prevent the compression of neural structures by postsurgical fibrosis. Methods: In this study, a new bacterial cellulose (BC) anti-adhesion membrane, composed of exosomes from human umbilical cord mesenchymal stem cells, was developed. Its structure and morphology, water content, thickness, and mechanical properties of elasticity were analyzed and characterized. The degradation of the BC+exosomes (BC+Exos) membrane in vitro was evaluated, and its in vitro cytotoxicity and in vivo biocompatibility were tested. The prevention effect of BC+Exos membrane on epidural fibrosis post-laminectomy in a rabbit model was investigated. Results: The BC+Exos membrane showed a three-dimensional network structure constituted of high-purity cellulose and moderate mechanical properties. No degeneration was observed. The BC+Exos membrane showed no cytotoxicity and displayed biocompatibility in vivo. The BC+Exos film was able to inhibit epidural fibrosis and peridural adhesions. Conclusion: Based on the current findings, the BC+Exos membrane is a promising material to prevent postoperative epidural fibrosis and adhesion. Keywords: failed back surgery syndrome, epidural fibrosis, adhesion, human umbilical cord mesenchymal stem cell, exosome, bacterial cellulose

Y Grace Wang,1 Khadra Benmedjahed,2 Jérémy Lambert,2 Christopher J Evans,3 Steve Hwang,3 Jed Black,1,4 Murray W Johns5 1Clinical Development, Jazz Pharmaceuticals, Palo Alto, CA, USA; 2Patient-Centered Outcomes, Mapi, Lyon, France; 3Endpoint Outcomes, Boston, MA, USA; 4Sleep Medicine, Stanford Sleep Medicine Center, Redwood City, CA, USA; 5Epworth Sleep Centre, East Melbourne, VIC, Australia Objective: The aim of this study was to qualitatively evaluate concepts for incorporation into a daily diary to capture cataplexy frequency and to assess the content validity of the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) in pediatric patients with narcolepsy.Patients and methods: Face-to-face concept elicitation and cognitive interviews were conducted with children (7–9 years; n=13) and adolescents (10–17 years; n=16) who have narcolepsy with cataplexy, and their parents/caregivers.Results: Similarities and differences were noted between narcolepsy concepts described by children and their parents/caregivers, suggesting some different but complementary perspectives; parents may not recognize cataplexy symptoms/triggers as well as children, but parents have greater recognition of the circumstances of falling asleep. Cataplexy diary modifications included changes in definitions and examples of cataplexy, using child-friendly terminology, adding a quantitative question to determine daily frequency, and standardizing the questionnaire for evening administration with self-completion by the child. Modifications were made to ESS-CHAD for child-friendly wording and to ensure that items reflect activities (eating, watching TV/video) and environments (school, bus/car transport) in which children are likely to participate. Two ESS-CHAD versions were proposed: one with a 1-month recall period, for general use, and the other with a recall period of “since your last study visit,” for research, which could be shorter or longer than 1 month (as short as 1 week).Conclusion: The cataplexy diary and ESS-CHAD were modified for the assessment of children and adolescents. Further psychometric validation is recommended. These measures are being used in a Phase III, placebo-controlled clinical trial of sodium oxybate in children and adolescents with narcolepsy. Keywords: narcolepsy, cataplexy, sleepiness, assessment, children, adolescents

Li-Yao Zhu,1,* Yu-Gang Wang,2,* Li-Qing Wei,3,* Jian Zhou,1 Wei-Jie Dai,4 Xiao-Yu Zhang5,6 1Department of Hepatology, The Fourth People’s Hospital of Huai’an, Huai’an, Jiangsu, 2Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 3Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 4Department of Gastroenterology, Huai’an First People’s Hospital, Nanjing Medical University, 5Division of Gastrointestinal Surgery, Department of General Surgery, The Affiliated Huai’an Hospital of Xuzhou Medical College, 6Division of Gastrointestinal Surgery, Department of General Surgery, The Second People’s Hospital of Huai’an, Huai’an, Jiangsu, People’s Republic of China *These authors contributed equally to this work Purpose: To further observe and verify the effect of nonalcoholic fatty liver disease (NAFLD) on the response to antiviral therapy in patients with chronic hepatitis B (CHB) and investigate the relationship between the virologic response and insulin resistance. Patients and methods: A retrospective study was adopted and 61 NAFLD patients with HBeAg-positive CHB were included as the observation group (group A), and 64 patients with simple CHB were included as the control group (group B). Results: After 12 weeks of treatment with entecavir, the total virologic response rate in group A was statistically significantly lower than that in group B (P0.05). In weeks 48 and 96, there was no significant difference in the HBeAg seroconversion rates between the two groups (P>0.05). In weeks 12 and 24, there was also no significant difference in the alanine transaminase (ALT) normalization rate between the two groups (P>0.05). Then, in weeks 48 and 96, the ALT normalization rate of group A was obviously lower than that of group B (PM) according to the median value (M=2.79) of the baseline homeostatic model assessment method insulin resistance levels. In weeks 48 and 96, the ALT normalization rate of group A1 was significantly higher than that of group A2 (P

Ying Yang,1 Hai-yong Ao,1 Sheng-bing Yang,1 Yu-gang Wang,1 Wen-tao Lin,2 Zhi-feng Yu,1 Ting-ting Tang1 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 2Department of Orthopedics, Fuzhou Second Hospital, Affiliated Hospital of Xiamen University, Fuzhou, People’s Republic of China Abstract: Titanium-based implants have been widely used in orthopedic surgery; however, failures still occur. Our in vitro study has demonstrated that gentamicin-loaded, 80 nm-diameter nanotubes possessed both antibacterial and osteogenic activities. Thus, the aim of this study was to further investigate the in vivo anti-infection effect of the titanium implants with gentamicin-loaded nanotubes. Thirty-six male Sprague Dawley rats were used to establish an implant-associated infection model. A volume of 50 µL Staphylococcus aureus suspension (1×105 CFU/mL) was injected into the medullary cavity of the left femur, and then the titanium rods without modification (Ti), titanium nanotubes without drug loading (NT), and gentamicin-loaded titanium nanotubes (NT-G) were inserted with phosphate-buffered saline-inoculated Ti rods as a blank control. X-ray images were obtained 1 day, 21 days, and 42 days after surgery; micro-computed tomography, microbiological, and histopathological analyses were used to evaluate the infections at the time of sacrifice. Radiographic signs of bone infection, including osteolysis, periosteal reaction, osteosclerosis, and damaged articular surfaces, were demonstrated in the infected Ti group and were slightly alleviated in the NT group but not observed in the NT-G group. Meanwhile, the radiographic and gross bone pathological scores of the NT-G group were significantly lower than those of the infected Ti group (P

Rui Ma,1 Songchao Tang,2 Honglue Tan,1 Wentao Lin,1 Yugang Wang,1 Jie Wei,2 Liming Zhao,2 Tingting Tang1 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 2Key Laboratory for Ultrafine Materials of Ministry of Education and The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China Abstract: A bioactive composite was prepared by incorporating 40 wt% nano-­hydroxyapatite (nHA) into polyetheretherketone (PEEK) through a process of compounding, injection, and molding. The mechanical and surface properties of the nHA/PEEK composite were characterized, and the in vitro osteoblast functions in the composite were investigated. The mechanical properties (elastic modulus and compressive strength) of the nHA/PEEK composite increased significantly, while the tensile strength decreased slightly as compared with PEEK. Further, the addition of nHA into PEEK increased the surface roughness and hydrophilicity of the nHA/PEEK composite. In cell tests, compared with PEEK and ultra-high-molecular-weight polyethylene, it was found that the nHA/PEEK composite could promote the functions of MC3T3-E1 cells, including cell attachment, spreading, proliferation, alkaline phosphatase activity, calcium nodule formation, and expression of osteogenic differentiation-related genes. Incorporation of nHA into PEEK greatly improved the bioperformance of PEEK. The nHA/PEEK composite might be a promising orthopedic implant material. Keywords: polyetheretherketone, nano-hydroxyapatite, biocomposite, osteoblast functions, orthopedic implant material

Shefang Ye,1 Min Chen,1 Yuanqin Jiang,1,2 Mingliang Chen,3 Tong Zhou,1 Yange Wang,1 Zhenqing Hou,1 Lei Ren11Department of Biomaterials, Research Center of Biomedical Engineering, College of Materials, Xiamen University, Xiamen, People's Republic of China; 2First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China; 3Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration, Xiamen, People's Republic of ChinaAbstract: Polyhydroxylated derivatives of fullerene C60, named fullerenols (C60[OH]n), have stimulated great interest because of their potent antioxidant properties in various chemical and biological systems, which enable them to be used as a new promising pharmaceutical for the future treatment of oxidative stress-related diseases, but the details remain unknown. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a principal transcription factor that regulates expression of several antioxidant genes via binding to the antioxidant response element and plays a crucial role in cellular defence against oxidative stress. In this study we investigated whether activation of the Nrf2/antioxidant response element pathway contributes to the cytoprotective effects of C60(OH)24. Our results showed that C60(OH)24 enhanced nuclear translocation of Nrf2 and upregulated expression of phase II antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1, and γ-glutamate cysteine ligase in A549 cells. Treatment with C60(OH)24 resulted in phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK), extracellular signal-regulated kinases, and c-Jun-N-terminal kinases. By using inhibitors of cellular kinases, we showed that pretreatment of A549 cells with SB203580, a specific inhibitor of p38 MAPK, abolished nuclear translocation of Nrf2 and induction of HO-1 protein induced by C60(OH)24, indicating an involvement of p38 MAPK in Nrf2/HO-1 activation by C60(OH)24. Furthermore, pretreatment with C60(OH)24 attenuated hydrogen peroxide-induced apoptotic cell death in A549 cells, and knockdown of Nrf2 by small interfering ribonucleic acid diminished C60(OH)24-mediated cytoprotection. Taken together, these findings demonstrate that C60(OH)24 may attenuate oxidative stress-induced apoptosis via augmentation of Nrf2-regulated cellular antioxidant capacity, thus providing insights into the mechanisms of the antioxidant properties of C60(OH)24.Keywords: fullerenol, Nrf2, oxidative stress, cytoprotection, A549 cells

A Fresnel zoneplate is a diffractive optical element consisting of concentric rings (zones) for which the transmitted light produces a focal spot that is used in all wavelength regimes, including X-rays. The pattern of transmission openings determines the location of the spot and the sub-half wavelength size of the openings can adjust the intensity. Today, very general transmission zoneplate patterns are used for many special imaging and image compensation purposes. Manufacturing zoneplates require a zoneplate pattern file, which precisely describes the size, shape, and contour of the rings based on the desired optical properties of the lens. Generating such a pattern requires the delicate balance of achieving the required optical performance while maintaining manageable file sizes and computation times. Here we describe a new algorithm meeting these needs. By precisely controlling the number of shapes in each zone, the algorithm simultaneously optimizes the desired optical tolerances with the pattern file size.

The SHARP high-numerical aperture actinic reticle review project is a synchrotron-based, extreme ultraviolet (EUV) microscope dedicated to photomask research. SHARP emulates the illumination and imaging conditions of current EUV lithography scanners and those several generations into the future. An anamorphic imaging optic with increased mask-side numerical aperture (NA) in the horizontal and increased demagnification in the vertical direction has been proposed to overcome limitations of current multilayer coatings and extend EUV lithography beyond 0.33 NA. Zoneplate lenses with an anamorphic 4×/8× NA of 0.55 are fabricated and installed in the SHARP microscope to emulate anamorphic imaging. SHARP's Fourier synthesis illuminator with a range of angles exceeding the collected solid angle of the newly designed elliptical zoneplates can produce arbitrary angular source spectra matched to anamorphic imaging. A target with anamorphic dense features down to 50-nm critical dimension is fabricated using 40 nm of nickel as the absorber. In a demonstration experiment, anamorphic imaging at 0.55 4×/8× NA and 6 deg central ray angle (CRA) is compared with conventional imaging at 0.5 4× NA and 8 deg CRA. A significant contrast loss in horizontal features is observed in the conventional images. The anamorphic images show the same image quality in the horizontal and vertical directions.

In this article, procedure and efficiency of the reduced-basis approach in structural design computation are studied. As a model order reduction approach, it provides fast evaluation of a structural system in explicitly parameterized formulation. Theoretically, the original structural system is reduced to obtain a reduced system by being projected onto a lower dimensional subspace. However, in practice, it is a time-consuming process due to the iterations of adaptive procedure in subspace construction. To improve the efficiency of the method, some characteristics are analyzed. First, the accuracy of the subspace is evaluated and computational costs of procedures with different approaches are studied. Results show that the subspaces constructed by greedy adaptive procedures with different beginnings have the same accuracy. It is instructive that accuracy of the subspace is guaranteed by adaptive procedure. And the computational costs depend on the number of iterations in adaptive procedure. Thus, a modified adaptive procedure is proposed to reduce the computational costs and guarantee the accuracy. The modified adaptive procedure begins with experimental design methods to obtain a set of samples rather than a single sample and ends with the adaptive procedure. The start set of samples are selected by the following experimental design methods: 2k factorial design, standard Latin design and Latin hypercube design. By being integrated with the experimental design, the modified adaptive procedure saves computational costs and retains the same accuracy as traditional procedure does. As an example, the outputs of a vehicle body front compartment subjected to a bending load are illustrated. It is proved that the proposed procedure is efficient and is applicable to many other structural design contexts. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE: To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN: Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING: Eleven hospitals from 4 provinces in China. PATIENTS: 410 young adults aged 15 to 59 years with laboratory-confirmed H1N1 influenza. INTERVENTION: Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS: Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS: Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS: Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION: Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE: Beijing Science and Technology Project and Beijing Nova Program. [ABSTRACT FROM AUTHOR]