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Background: The purpose of this study was to design a customized fixation plate for mandibular angle fracture using topological optimization based on the biomechanical properties of the two conventional fixation systems, and compare the results of stress, strain and displacement distributions calculated by finite element analysis (FEA).Methods: A three-dimensional (3D) virtual mandible was reconstructed from CT images with a mimic angle fracture and a 1 mm gap between two bone segments, and then a FEA model, including volume mesh with inhomogeneous bone material properties, three loading conditions and constraints (muscles and condyles), was created to design a customized plate using topological optimization method, then the shape of the plate was referenced from the stress concentrated area on an initial part created from thickened bone surface for optimal calculation, and then the plate was formulated as "V" pattern according to dimensions of standard mini-plate finally. To compare the biomechanical behavior of the "V" plate and other conventional mini-plates for angle fracture fixation, two conventional fixation systems were used: type A, one standard mini-plate, and type B, two standard mini-plates, and the stress, strain and displacement distributions within the three fixation systems were compared and discussed.Results: The stress, strain and displacement distributions to the angle fractured mandible with three different fixation modalities were collected, respectively, and the maximum stress for each model emerged at the mandibular ramus or screw holes. Under the same loading conditions, the maximum stress on the customized fixation system decreased 74.3, 75.6 and 70.6% compared to type A, and 34.9, 34.1, and 39.6% compared to type B. All maximum von Mises stresses of mandible were well below the allowable stress of human bone, as well as maximum principal strain. And the displacement diagram of bony segments indicated the effect of treatment with different fixation systems.Conclusions: The customized fixation system with topological optimized structure has good biomechanical behavior for mandibular angle fracture because the stress, strain and displacement within the plate could be reduced significantly comparing to conventional "one mini-plate" or "two mini-plates" systems. The design methodology for customized fixation system could be used for other fractures in mandible or other bones to acquire better mechanical behavior of the system and improve stable environment for bone healing. And together with SLM, the customized plate with optimal structure could be designed and fabricated rapidly to satisfy the urgent time requirements for treatment. [ABSTRACT FROM AUTHOR]

Background: Neovascular glaucoma is a refractive glaucoma. Recently, anti-VEGF factors have been used alone or in combination for the treatment of neovascular glaucoma. However, the medium- and long-term efficacy of such drugs remains to be evaluated. This study was to determine the efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma.Methods: In this prospective non-randomized study, 43 neovascular glaucoma patients (43 eyes) were assigned to receive either 0.5 mg intravitreal ranibizumab for three to 14 days before Ahmed glaucoma valve implantation (injection group, n = 21) or Ahmed glaucoma valve implantation alone (control group, n = 22). The patients were followed up for six to 12 months. Differences in surgical success rate, intraocular pressure, best corrected visual acuity, anti-glaucoma medications and postoperative complications were compared between the two groups. Surgical success was defined as IOP > = 6 mm Hg and < = 21 mm Hg, with or without the use of anti-glaucoma medications, and without severe complications or reoperation.Results: Of the 43 patients, 40 completed the 6-month follow-up and 37 completed the 1-year follow-up. Success rate was 73.7% vs. 71.4% at six months and 72.2% vs. 68.4% at 12 months in the injection group and the control group respectively. No significant difference was noted between the two groups (six months: P = 0.87, 12 months: P = 1.00). There were no significant differences in the two groups with respect to intraocular pressure, best corrected visual acuity, anti-glaucoma medications or postoperative complications at six months or 12 months.Conclusions: Single intravitreal ranibizumab (0.5 mg) before surgery has no significant effect on the medium- or long-term outcomes of neovascular glaucoma treated with Ahmed glaucoma valve implantation.Trial Registration: Chinese Clinical Trial Registry ( ChiCTR-OOC-14005709, Trial registration date: 2014-12-01). [ABSTRACT FROM AUTHOR]

Background: Evidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity. To further test the cellular and molecular changes underlying analgesic effect of acupuncture, the global change of acupuncture associated protein profiles in the hippocampus under neuropathic pain condition was profiled.Methods: The chronic constrictive injury (CCI) model was established by ligature of the unilateral sciatic nerve in adult Wistar rats. Rats were randomized into normal control (NC) group, CCI group, and CCI withelectroacupuncture (EA) stimulation group. EA was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) in the EA group. Differentially expressed proteins in the hippocampus in the three groups were identified by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering of the identified proteins was analyzed by Mascot software.Results: After CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of acupuncture treatment. Following EA, there were 19 hippocampal proteins identified with significant changes in expression (>2-fold), which are involved in metabolic, physiological, and cellular processes. The top three canonical pathways identified were “cysteine metabolism”, “valine, leucine, and isoleucinedegradation” and “mitogen-activated protein kinase (MAPK) signaling”.Conclusions: These data suggest that the analgesic effect of EA is mediated by regulation of hippocampal proteins related to amino acid metabolism and activation of the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Infection with high-risk human papillomavirus is an important factor associated with cervical cancer, and the distribution of HPV types varies greatly worldwide. Determination of typespecific HPV prevalence constitutes an important step towards the development of vaccines for the prevention of cervical cancer. Methods: The human papillomavirus (HPV) genotypes in 190 cervical cancer specimens taken from the Sichuan province, the most populous province of Southwest China, were detected by a combination of MY09/11 consensus primers PCR (MY09/11 PCR), type-specific primers one-step PCR (One-step TS PCR) and E6/E7 gene type-specific primers nested PCR (Nested TS PCR). The prevalence and distribution of HPV in patients with cervical cancer, especially for HPV types 16, 18, 52, 58 and 59, suspected to be most common in certain parts of China, was investigated. Results: The HPV infection rates detected by MY09/11 PCR, One-step TS PCR and Nested TS PCR were 159 (83.7%), 145 (76.3%) and 172 (90.5%), respectively. The overall HPV prevalence was 93.2% (177/190). The positive specimens for HPV16, 18, 52, 58 and 59 detected by One-step TSPCR were 111 (58.4%), 14 (7.4%), 6 (3.2%), 13 (6.8%) and 4 (2.1%), respectively. By Nested TSPCR analysis, the detection rates of HPV16, 52, 58 and 59 were increased to 140 (73.7%), 30 (15.8%), 37 (19.5%) and 25 (13.2%), while only 4 (2.1%) additional specimens were found to be infected with HPV18. Conclusion: Our data demonstrate that, besides HPV 16, which was found to be the most prevalent type, HPV types 58, 52 and 59 are more prevalent than HPV18 in women with cervical cancer in the Sichuan area of China. [ABSTRACT FROM AUTHOR]

Background: Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer (TNBC). Hence, autophagy-related gene 5 (ATG5), an essential molecule involved in autophagy regulation, is presumably associated with recurrence of TNBC. This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival (DFS) of early-stage TNBC patients treated with anthracycline- and/or taxane-based chemotherapy., Methods: We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline- and/or taxane-based chemotherapy using the sequenom's MassARRAY system. Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients., Results: Three genotypes, AA, GA, and GG, were detected in the rs473543 of ATG5 gene. The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence (P = 0.024). Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543 (P = 0.034). In addition, after adjusting for clinical factors, multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS (hazard risk [HR], 1.73; 95% confidence interval [CI], 1.04-2.87; P = 0.034). In addition, DFS was shorter in node-negative patients with the presence of A allele (AA/GA) than in those with the absence of A allele (P = 0.027)., Conclusion: ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.

Background: The purpose of this study was to design a customized fixation plate for mandibular angle fracture using topological optimization based on the biomechanical properties of the two conventional fixation systems, and compare the results of stress, strain and displacement distributions calculated by finite element analysis (FEA)., Methods: A three-dimensional (3D) virtual mandible was reconstructed from CT images with a mimic angle fracture and a 1 mm gap between two bone segments, and then a FEA model, including volume mesh with inhomogeneous bone material properties, three loading conditions and constraints (muscles and condyles), was created to design a customized plate using topological optimization method, then the shape of the plate was referenced from the stress concentrated area on an initial part created from thickened bone surface for optimal calculation, and then the plate was formulated as "V" pattern according to dimensions of standard mini-plate finally. To compare the biomechanical behavior of the "V" plate and other conventional mini-plates for angle fracture fixation, two conventional fixation systems were used: type A, one standard mini-plate, and type B, two standard mini-plates, and the stress, strain and displacement distributions within the three fixation systems were compared and discussed., Results: The stress, strain and displacement distributions to the angle fractured mandible with three different fixation modalities were collected, respectively, and the maximum stress for each model emerged at the mandibular ramus or screw holes. Under the same loading conditions, the maximum stress on the customized fixation system decreased 74.3, 75.6 and 70.6% compared to type A, and 34.9, 34.1, and 39.6% compared to type B. All maximum von Mises stresses of mandible were well below the allowable stress of human bone, as well as maximum principal strain. And the displacement diagram of bony segments indicated the effect of treatment with different fixation systems., Conclusions: The customized fixation system with topological optimized structure has good biomechanical behavior for mandibular angle fracture because the stress, strain and displacement within the plate could be reduced significantly comparing to conventional "one mini-plate" or "two mini-plates" systems. The design methodology for customized fixation system could be used for other fractures in mandible or other bones to acquire better mechanical behavior of the system and improve stable environment for bone healing. And together with SLM, the customized plate with optimal structure could be designed and fabricated rapidly to satisfy the urgent time requirements for treatment.

Background: The relationship between non-fasting remnant cholesterol and cardiovascular outcome in the era of potent statin therapy remained to be elucidated., Methods: A cohort study of three hundred and twenty eight diabetics diagnosed with new-onset stable coronary artery disease (CAD) by coronary angiography were enrolled. All cases were followed up for an average duration of twelve months. The association between baseline remnant cholesterol levels and major cardiovascular outcomes were evaluated using the receivers operating characteristic (ROC) curves and Cox proportional hazards regression analysis., Results: During a period of 12-month's follow-up, 14.3% patients (47/328) underwent pre-specified adverse outcomes. The remnant cholesterol associated with high sensitivity C-reactive protein, neutrophil count and fibrinogen (R 2  = 0.20, 0.12 and 0.14; P = 0.000, 0.036 and 0.010 respectively). Area under the ROC curves (AUC) indicated discriminatory power of the remnant cholesterol to predict the adverse outcomes for this population (AUC = 0.64, P < 0.005). Kaplan-Meier curve suggested that the lower levels of remnant cholesterol showed relatively lower cardiac events for diabetic patients with stable CAD (Log rank X 2  = 8.94, P = 0.04). However, according to multivariate Cox proportional hazards regression, apart from hemoglobin A1C (Hazard ratio [H.R.] =1.38, 95% CI: 1.14-1.66, P = 0.001) and Gensini scores (H.R. = 1.00, 95% CI: 1.00-1.02; P = 0.035), remnant cholesterol did not qualify as an independent predictor of adverse prognosis in these settings (H.R. = 1.05, 95% CI: 0.46-2.37, P = 0.909)., Conclusions: Non-fasting remnant cholesterol was associated with inflammatory biomarkers and high incidence of revascularization, but not qualified as an independent predictor for short-term prognosis of diabetics with new-onset stable coronary artery disease.

Background: Both hormonal therapy (HT) and maintenance capecitabine monotherapy (MCT) have been shown to extend time to progression (TTP) in patients with metastatic breast cancer (MBC) after failure of taxanes and anthracycline-containing regimens. However, no clinical trials have directly compared the efficacy of MCT and HT after response to first-line capecitabine-based combination chemotherapy (FCCT) in patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer., Methods: We retrospectively analyzed the charts of 138 HR-positive and HER2-negative MBC patients who were in non-progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences, in Beijing, China. The median number of first-line chemotherapy cycles was 6 (range, 4-8); combined agents included taxanes, vinorelbine, or gemcitabine. Of these 138 patients, 79 received MCT, and 59 received HT. Single-agent capecitabine was administered at a dose of 1250 mg/m(2) twice daily for 14 days, followed by a 7-day rest period, repeated every 3 weeks. Of the 59 patients who received HT, 37 received aromatase inhibitors (AIs), 8 received selective estrogen receptor modulators (SERMs), and 14 received goserelin plus either AIs or SERMs. We then compared the MCT group and HT group in terms of treatment efficacy., Results: With a median follow-up of 43 months, patients in the HT group had a much longer TTP than patients in the MCT group (13 vs. 8 months, P = 0.011). When TTP was adjusted for age, menopausal status, Karnofsky performance status score, disease-free survival, site of metastasis, number of metastatic sites, and response status after FCCT, extended TTP was still observed for patients in the HT group (hazard ratio: 0.63; 95% confidence interval: 0.44-0.93; P = 0.020). We also observed a trend of overall survival advantage for patients in the HT group vs. patients in the MCT group, but the difference was not significant (43 vs. 37 months, P = 0.400). In addition, patients in the HT group generally tolerated the treatment well, whereas patients in the MCT group experienced grades 3-4 adverse events, the most frequent of which were hand-foot syndrome (15.8%) and hematologic abnormalities (7.6%)., Conclusion: For HR-positive and HER2-negative MBC patients, HT might be considered a treatment after response to FCCT but prior to MCT as a long-term administration.

Background: Diabetic nephropathy is one of the most serious complications in patients with diabetes. At present, there are no satisfactory treatments available for diabetic nephropathy. Stem cells are currently the main candidates for the development of new treatments for diabetic nephropathy, as they may exert their therapeutic effects mainly through paracrine mechanisms. Exosomes derived from stem cells have been reported to play an important role in kidney injury. In this article, we try to investigate whether exosomes retrieved from urine stem cells could itself prevent diabetic nephropathy at an early stage in vivo and in vitro., Methods: Exosomes from conditioned medium of urine-derived stem cells (USCs-Exo) were isolated using ultrafiltration-combined purification methods. USCs-Exo were then verified by morphology, size, and specific biomarkers using transmission electron microscopy, tunable resistive pulse sensing analysis, and western blotting. After establishment of the streptozotocin-induced Sprague-Dawley rat model, the effects of USCs-Exo on kidney injury and angiogenesis were observed via weekly tail intravenous injection of USCs-Exo or control until 12 weeks. In vitro, podocytes cultured in high-glucose medium were treated with USCs-Exo to test the protective effect of USCs-Exo on podocytic apoptosis. Meanwhile, the potential factors in promoting vascular regeneration in USCs-Exo and urine-derived stem cell conditioned medium were investigated by enzyme-linked immunosorbent assay., Results: Urine-derived stem cells were cultured and were verified by positive markers for CD29, CD73, CD90 and CD44 antigens, and negative markers for CD34, CD45 and HLA-DR. USCs-Exo were approximately 50-100 nm spherical vesicles, and the specific markers included CD9, CD63 and CD81. Intravenous injections of USCs-Exo could potentially reduce the urine volume and urinary microalbumin excretion, prevent podocyte and tubular epithelial cell apoptosis, suppress the caspase-3 overexpression and increase glomerular endothelial cell proliferation in diabetic rats. In addition, USCs-Exo could reduce podocytic apoptosis induced by high glucose in vitro. USCs-Exo contained the potential factors, including growth factor, transforming growth factor-β1, angiogenin and bone morphogenetic protein-7, which may be related with vascular regeneration and cell survival., Conclusion: USCs-Exo may have the potential to prevent kidney injury from diabetes by inhibiting podocyte apoptosis and promoting vascular regeneration and cell survival.

Background: Neovascular glaucoma is a refractive glaucoma. Recently, anti-VEGF factors have been used alone or in combination for the treatment of neovascular glaucoma. However, the medium- and long-term efficacy of such drugs remains to be evaluated. This study was to determine the efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma., Methods: In this prospective non-randomized study, 43 neovascular glaucoma patients (43 eyes) were assigned to receive either 0.5 mg intravitreal ranibizumab for three to 14 days before Ahmed glaucoma valve implantation (injection group, n = 21) or Ahmed glaucoma valve implantation alone (control group, n = 22). The patients were followed up for six to 12 months. Differences in surgical success rate, intraocular pressure, best corrected visual acuity, anti-glaucoma medications and postoperative complications were compared between the two groups. Surgical success was defined as IOP > = 6 mm Hg and < = 21 mm Hg, with or without the use of anti-glaucoma medications, and without severe complications or reoperation., Results: Of the 43 patients, 40 completed the 6-month follow-up and 37 completed the 1-year follow-up. Success rate was 73.7% vs. 71.4% at six months and 72.2% vs. 68.4% at 12 months in the injection group and the control group respectively. No significant difference was noted between the two groups (six months: P = 0.87, 12 months: P = 1.00). There were no significant differences in the two groups with respect to intraocular pressure, best corrected visual acuity, anti-glaucoma medications or postoperative complications at six months or 12 months., Conclusions: Single intravitreal ranibizumab (0.5 mg) before surgery has no significant effect on the medium- or long-term outcomes of neovascular glaucoma treated with Ahmed glaucoma valve implantation., Trial Registration: Chinese Clinical Trial Registry ( ChiCTR-OOC-14005709, Trial registration date: 2014-12-01).

Background: Recently it was suggested that high myopia macular holes (HMMH) and macular holes accompanied by retinal detachment occur in the advanced stages of myopia traction maculopathy (MTM), while macular retinoschisis, shallow retinal detachment without holes, and lamellar macular holes occur in the early stages of MTM. Complete vitreous cortex removal associated with internal limiting membrane peeling is now widely used to treat HMMH. However, it remains uncertain at what HMMH stage patients would benefit most from surgical intervention. Our study was aimed to evaluate the postoperative anatomical changes and functional outcomes of high myopia macular holes (HMMH)., Methods: Patients were retrospectively collected between March 2009 and August 2011. Before and 1st, 3rd, and 9th month after 23G pars plana vitrectomy, all patients underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT) and MP-1. At each follow-up, best-corrected visual acuity (BCVA), photoreceptor inner and outer segments (IS/OS) defects, and retinal sensitivity (RS) were investigated. According to different preoperative macular hole morphologies, patients were divided into three groups: Group 1, macular hole with epiretinal membrane (ERM) traction and macular retinoschisis; Group 2, full-thickness macular hole (FTMH); Group 3, FTMH with subretinal fluid., Results: 43 eyes from 43 patients met the inclusion criteria. The mean age was 60 years. BCVA and RS were significantly improved after vitrectomy; the mean IS/OS defect was significantly reduced. At 9 postoperative months, 11 of 43 (25.6 %) eyes achieved IS/OS junction integrity; 9 of these 11 (81.8 %) eyes belonged to Group 1, 2 (18.2 %) belonged to Group 2., Conclusions: Pars plana vitrectomy combined with ILM peeling and gas tamponade results in limited functional outcomes in patients with HMMH. The appearance of subretinal fluid indicates a worse prognosis for surgical intervention.

Background: Biological nitrogen fixation is highly controlled at the transcriptional level by regulatory networks that respond to the availability of fixed nitrogen. In many diazotrophs, addition of excess ammonium in the growth medium results in immediate repression of nif gene transcription. Although the regulatory cascades that control the transcription of the nif genes in proteobacteria have been well investigated, there are limited data on the kinetics of ammonium-dependent repression of nitrogen fixation., Results: Here we report a global transcriptional profiling analysis of nitrogen fixation and ammonium repression in Pseudomonas stutzeri A1501, a root-associated and nitrogen-fixing bacterium. A total of 166 genes, including those coding for the global nitrogen regulation (Ntr) and Nif-specific regulatory proteins, were upregulated under nitrogen fixation conditions but rapidly downregulated as early as 10 min after ammonium shock. Among these nitrogen fixation-inducible genes, 95 have orthologs in each of Azoarcus sp. BH72 and Azotobacter vinelandii AvoP. In particular, a 49-kb expression island containing nif and other associated genes was markedly downregulated by ammonium shock. Further functional characterization of pnfA, a new NifA-sigma54-dependent gene chromosomally linked to nifHDK, is reported. This gene encodes a protein product with an amino acid sequence similar to that of five hypothetical proteins found only in diazotrophic strains. No noticeable differences in the transcription of nifHDK were detected between the wild type strain and pnfA mutant. However, the mutant strain exhibited a significant decrease in nitrogenase activity under microaerobic conditions and lost its ability to use nitrate as a terminal electron acceptor for the support of nitrogen fixation under anaerobic conditions., Conclusions: Based on our results, we conclude that transcriptional regulation of nif gene expression in A1501 is mediated by the nif-specific and ntr gene regulatory systems. Furthermore, microarray and mutational analyses revealed that many genes of unknown function may play some essential roles in controlling the expression or activity of nitrogenase. The findings presented here establish the foundation for further studies on the physiological function of nitrogen fixation-inducible genes.