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1.  Identification and Classification of Rhizobia by Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry 
Mass spectrometry (MS) has been widely used for specific, sensitive and rapid analysis of proteins and has shown a high potential for bacterial identification and characterization. Type strains of four species of rhizobia and Escherichia coli DH5α were employed as reference bacteria to optimize various parameters for identification and classification of species of rhizobia by matrix-assisted laser desorption/ionization time-of-flight MS (MALDI TOF MS). The parameters optimized included culture medium states (liquid or solid), bacterial growth phases, colony storage temperature and duration, and protein data processing to enhance the bacterial identification resolution, accuracy and reliability. The medium state had little effects on the mass spectra of protein profiles. A suitable sampling time was between the exponential phase and the stationary phase. Consistent protein mass spectral profiles were observed for E. coli colonies pre-grown for 14 days and rhizobia for 21 days at 4°C or 21°C. A dendrogram of 75 rhizobial strains of 4 genera was constructed based on MALDI TOF mass spectra and the topological patterns agreed well with those in the 16S rDNA phylogenetic tree. The potential of developing a mass spectral database for all rhizobia species was assessed with blind samples. The entire process from sample preparation to accurate identification and classification of species required approximately one hour.
PMCID: PMC4616259  PMID: 26500417
Bacterial identification; Bacterial classification; MALDI TOF MS; Rhizobium
2.  Percutaneous balloon kyphoplasty for the treatment of vertebral compression fractures 
BMC Surgery  2014;14:3.
Vertebral compression fractures (VCFs) constitute a major health care problem, not only because of their high incidence but also because of their direct and indirect negative impacts on both patients’ health-related quality of life and costs to the health care system. Two minimally invasive surgical approaches were developed for the management of symptomatic VCFs: balloon kyphoplasty and vertebroplasty. The purpose of this study was to evaluate the effectiveness and safety of balloon kyphoplasty in the treatment of symptomatic VCFs.
Between July 2011 and June 2012, one hundred and eighty-seven patients with two hundred and fifty-one vertebras received balloon kyphoplasty in our hospital. There were sixty-five male and one hundred and twenty-two female patients with an average age of 74.5 (range, 61 to 95 years). The pain symptoms and quality of life, were measured before operation and at one day, three months, six months and one year following kyphoplasty. Radiographic data including restoration of kyphotic angle, anterior vertebral height, and any leakage of cement were defined.
The mean visual analog pain scale decreased from a preoperative value of 7.7 to 2.2 at one day (p < .05) following operation and the Oswestry Disability Index improved from 56.8 to 18.3 (p < .05). The kyphotic angle improved from a mean of 14.4° before surgery to 6.7° at one day after surgery (p < .05). The mean anterior vertebral height increased significantly from 52% before surgery to 74.5% at one day after surgery (p < .05) and 70.2% at one year follow-up. Minor cement extravasations were observed in twenty-nine out of two hundred and fifty-one procedures, including six leakage via basivertebral vein, three leakage via segmental vein and twenty leakage through a cortical defect. None of the leakages were associated with any clinical consequences.
Balloon kyphoplasty not only rapidly reduced pain and disability but also restored sagittal alignment in our patients at one-year follow-up. The treatment of osteoporotic vertebral compression fractures with balloon kyphoplasty is a safe, effective, and minimally invasive procedure that provides satisfactory clinical results.
PMCID: PMC3922728  PMID: 24423182
3.  High-Resolution Transcriptomic Analyses of Sinorhizobium sp. NGR234 Bacteroids in Determinate Nodules of Vigna unguiculata and Indeterminate Nodules of Leucaena leucocephala 
PLoS ONE  2013;8(8):e70531.
The rhizobium-legume symbiosis is a model system for studying mutualistic interactions between bacteria and eukaryotes. Sinorhizobium sp. NGR234 is distinguished by its ability to form either indeterminate nodules or determinate nodules with diverse legumes. Here, we presented a high-resolution RNA-seq transcriptomic analysis of NGR234 bacteroids in indeterminate nodules of Leucaena leucocephala and determinate nodules of Vigna unguiculata. In contrast to exponentially growing free-living bacteria, non-growing bacteroids from both legumes recruited several common cellular functions such as cbb3 oxidase, thiamine biosynthesis, nitrate reduction pathway (NO-producing), succinate metabolism, PHB (poly-3-hydroxybutyrate) biosynthesis and phosphate/phosphonate transporters. However, different transcription profiles between bacteroids from two legumes were also uncovered for genes involved in the biosynthesis of exopolysaccharides, lipopolysaccharides, T3SS (type three secretion system) and effector proteins, cytochrome bd ubiquinol oxidase, PQQ (pyrroloquinoline quinone), cytochrome c550, pseudoazurin, biotin, phasins and glycolate oxidase, and in the metabolism of glutamate and phenylalanine. Noteworthy were the distinct expression patterns of genes encoding phasins, which are thought to be involved in regulating the surface/volume ratio of PHB granules. These patterns are in good agreement with the observed granule size difference between bacteroids from L. leucocephala and V. unguiculata.
PMCID: PMC3732241  PMID: 23936444
4.  Robust Markers Reflecting Phylogeny and Taxonomy of Rhizobia 
PLoS ONE  2012;7(9):e44936.
Genomic ANI (Average Nucleotide Identity) has been found to be able to replace DNA-DNA hybridization in prokaryote taxonomy. The ANI of each of the core genes that has a phylogeny congruent with the reference species tree of rhizobia was compared to the genomic ANI. This allowed us to identify three housekeeping genes (SMc00019-truA-thrA) whose ANI reflected the intraspecies and interspecies genomic ANI among rhizobial strains, revealing an ANI gap (≥2%) between the inter- and intra-species comparisons. The intraspecies (96%) and interspecies (94%) ANI boundaries calculated from three genes (SMc00019-truA-thrA) provided a criterion for bacterial species definition and confirmed 621/629 of known interspecies relationships within Bradyrhizobium, Mesorhizobium, Sinorhizobium and Rhizobium. Some widely studied strains should be renamed. The SMc00019-truA-thrA ANI also correlates well with the genomic ANI of strains in Agrobacterium, Methylobacterium, Ralstonia, Rhodopseudomonas, Cupriavidus and Burkholderia, suggesting their wide applicability in other bacteria.
PMCID: PMC3444505  PMID: 23028691
5.  Biodiversity and Biogeography of Rhizobia Associated with Soybean Plants Grown in the North China Plain ▿ †  
Applied and Environmental Microbiology  2011;77(18):6331-6342.
As the putative center of origin for soybean and the second largest region of soybean production in China, the North China Plain covers temperate and subtropical regions with diverse soil characteristics. However, the soybean rhizobia in this plain have not been sufficiently studied. To investigate the biodiversity and biogeography of soybean rhizobia in this plain, a total of 309 isolates of symbiotic bacteria from the soybean nodules collected from 16 sampling sites were studied by molecular characterization. These isolates were classified into 10 genospecies belonging to the genera Sinorhizobium and Bradyrhizobium, including four novel groups, with S. fredii (68.28%) as the dominant group. The phylogeny of symbiotic genes nodC and nifH defined four lineages among the isolates associated with Sinorhizobium fredii, Bradyrhizobium elkanii, B. japonicum, and B. yuanmingense, demonstrating the different origins of symbiotic genes and their coevolution with the chromosome. The possible lateral transfer of symbiotic genes was detected in several cases. The association between soil factors (available N, P, and K and pH) and the distribution of genospecies suggest clear biogeographic patterns: Sinorhizobium spp. were superdominant in sampling sites with alkaline-saline soils, while Bradyrhizobium spp. were more abundant in neutral soils. This study clarified the biodiversity and biogeography of soybean rhizobia in the North China Plain.
PMCID: PMC3187167  PMID: 21784912
6.  A Phase IIa Randomized, Double-Blind Trial of Erlotinib in Inhibiting Epidermal Growth Factor Receptor Signaling in Aberrant Crypt Foci of the Colorectum 
Colorectal cancer (CRC) progresses through multiple distinct stages that are potentially amenable to chemopreventative intervention. Epidermal Growth Factor Receptor (EGFR) inhibitors are efficacious in advanced tumors including CRC. There is significant evidence that EGFR also plays important roles in CRC initiation, and that EGFR inhibitors block tumorigenesis. We performed a double-blind randomized clinical trial to test whether the EGFR inhibitor erlotinib given for up to 30 days had an acceptable safety and efficacy profile to reduce EGFR signaling biomarkers in colorectal aberrant crypt foci (ACF), a subset of which progress to CRC, and normal rectal tissue. A total of N=45 patients were randomized to one of three erlotinib doses (25 mg, 50 mg, 100 mg) with randomization stratified by non-steroidal anti-inflammatory drug (NSAID) use. There were no unanticipated adverse events with Erlotinib therapy. Erlotinib was detected in both normal rectal mucosa and ACFs. Colorectal ACF phosphoERK, phosphoEGFR and total EGFR signaling changes from baseline were modest and there was no dose response. Overall, this trial did not meet is primary efficacy endpoint. Colorectal EGFR signaling inhibition by erlotinib is therefore likely insufficient to merit further studies without additional pre-screening stratification or potentially longer duration of use.
PMCID: PMC4355051  PMID: 25604134
7.  A replaceable liposomal aptamer for the ultrasensitive and rapid detection of biotin 
Scientific Reports  2016;6:21369.
Biotin is an essential vitamin which plays an important role for maintaining normal physiological function. A rapid, sensitive, and simple method is necessary to monitor the biotin level. Here, we reported a replacement assay for the detection of biotin using a replaceable liposomal aptamer. Replacement assay is a competitive assay where a sample analyte replaces the labeled competitor of analyte out of its biorecognition element on a surface. It is user friendly and time-saving because of washing free. We used aptamer as a competitor, not a biorecognition element as tradition. To label aptamers, we used cholesterol-conjugated aptamers to tag signal-amplifying-liposomes. Without the need of conjugation procedure, aptamers can be easily incorporated into the surface of dye-encapsulating liposomes. Two aptamers as competitors of biotin, ST-21 and ST-21M with different affinities to streptavidin, were studied in parallel for the detection of biotin using replacement assays. ST-21 and ST-21M aptamers reached to limits of detection of 1.32 pg/80 μl and 0.47 pg/80 μl, respectively. The dynamic ranges of our assays using ST-21 and ST-21M aptamers were seven and four orders of magnitude, respectively. This assay can be completed in 20 minutes without washing steps. These results were overall better than previous reported assays.
PMCID: PMC4763257  PMID: 26903199
8.  ATM-mediated PTEN phosphorylation promotes PTEN nuclear translocation and autophagy in response to DNA-damaging agents in cancer cells 
Autophagy  2015;11(2):239-252.
PTEN (phosphatase and tensin homolog), a tumor suppressor frequently mutated in human cancer, has various cytoplasmic and nuclear functions. PTEN translocates to the nucleus from the cytoplasm in response to oxidative stress. However, the mechanism and function of the translocation are not completely understood. In this study, topotecan (TPT), a topoisomerase I inhibitor, and cisplatin (CDDP) were employed to induce DNA damage. The results indicate that TPT or CDDP activates ATM (ATM serine/threonine kinase), which phosphorylates PTEN at serine 113 and further regulates PTEN nuclear translocation in A549 and HeLa cells. After nuclear translocation, PTEN induces autophagy, in association with the activation of the p-JUN-SESN2/AMPK pathway, in response to TPT. These results identify PTEN phosphorylation by ATM as essential for PTEN nuclear translocation and the subsequent induction of autophagy in response to DNA damage.
PMCID: PMC4502816  PMID: 25701194
ATM; autophagy; DNA damage; PTEN; topotecan; AKT/PKB, v-akt murine thymoma viral oncogene homolog; AMPK, protein kinase, AMP-activated; ATG, autophagy-related; ATM, ATM serine/threonine kinase; Baf.A1, bafilomycin A1; CASP3, caspase 3, apoptosis-related cysteine peptidase; CCND1, cyclin D1; CDDP, cisplatin; CENPC/CENP-C, centromere protein C; CITED1/p300/CBP, Cbp/p300-interacting transactivator, with Glu/Asp-rich C-terminal domain, 1; CSNK2/CK2, casein kinase 2; DSBs, DNA double-strand breaks; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFP, green fluorescent protein; GLTSCR2/PICT-1, glioma tumor suppressor candidate region gene 2; GSK3B, glycogen synthase kinase 3 β; GST, glutathione S-transferase; H2AFX; H2A histone family; member X; JUN; jun proto-oncogene; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; MTORC1, mechanistic target of rapamycin complex 1; MVP, major vault protein; NC, normal control; NEDD4, neural precursor cell expressed, developmentally down-regulated 4, E3 ubiquitin protein ligase; PAGE, polyacrylamide gel electrophoresis; PARP, poly (ADP-ribose) polymerase 1; PI3K, phosphoinositide 3-kinase; PMSF, phenylmethanesulfonyl fluoride; PPase, protein phosphatase; PtdIns(3, 4, 5)P3, phosphatidylinositol (3, 4, 5)-trisphosphate; PTEN, phosphatase and tensin homolog; RAD51, RAD51 recombinase; RPS6KB/p70S6K; ribosomal protein S6 kinase, 70kDa; SDS, sodium dodecyl sulfate; SESN2, sestrin 2; siRNA, small interfering RNA; SQSTM1/p62, sequestosome 1; TP53, tumor protein p53; TPT, topotecan; TUBA4A, tubulin, α, 4a; WT, wild type; YFP, yellow fluorescent protein
9.  Subtropical Potential Vorticity Intrusion Drives Increasing Tropospheric Ozone over the Tropical Central Pacific 
Scientific Reports  2016;6:21370.
Drawn from multiple reanalysis datasets, an increasing trend and westward shift in the number of Potential Vorticity intrusion events over the Pacific are evident. The increased frequency can be linked to a long-term trend in upper tropospheric equatorial westerly wind and subtropical jets during boreal winter to spring. These may be resulting from anomalous warming and cooling over the western Pacific warm pool and the tropical eastern Pacific, respectively. The intrusions brought dry and ozone rich air of stratospheric origin deep into the tropics. In the tropical upper troposphere, interannual ozone variability is mainly related to convection associated with El Niño/Southern Oscillation. Zonal mean stratospheric overturning circulation organizes the transport of ozone rich air poleward and downward to the high and midlatitudes leading there to higher ozone concentration. In addition to these well described mechanisms, we observe a long-term increasing trend in ozone flux over the northern hemispheric outer tropical (10–25°N) central Pacific that results from equatorward transport and downward mixing from the midlatitude upper troposphere and lower stratosphere during PV intrusions. This increase in tropospheric ozone flux over the Pacific Ocean may affect the radiative processes and changes the budget of atmospheric hydroxyl radicals.
PMCID: PMC4751467  PMID: 26868836
10.  Association between Social Integration and Health among Internal Migrants in ZhongShan, China 
PLoS ONE  2016;11(2):e0148397.
Internal migrants are the individuals who migrate between regions in one country. The number of internal migrants were estimated at 245 million in China in 2013. Results were inconsistent in the literature about the relationship between their health statuses and social integration. The main difference exists on how to measure the social integration and whether health statuses of internal migrants improve with years of residence. To complement the existing literature, this study measured social integration more comprehensively and estimated the internal migrants’ health statuses with varying years of residence, and explored the associations between the migrants’ social integration and health. We used the data from 2014 Internal Migrant Dynamic Monitoring Survey of Health and Family Planning in ZhongShan, China. Health status was measured from four aspects: self-reported health, subjective well-being, perception of stress, mental health. We measured social integration through four dimensions: economy, social communication, acculturation, and self-identity. The analyses used multiple linear regressions to examine the associations between self-reported health, subjective well-being, and perception of stress, mental health and social integration. The analytical sample included 1,999 households of the internal migrants and 1,997 local registered households, who were permanent residents in ZhongShan. Among the internal migrants, Adults in the labor force, who were aged 25 to 44 years old, accounted for 91.2% of the internal migrant population, while 74.6% of the registered population were in that age group. Median residential time among migrants was 2.8 (1.3–6.2) years, and 20.2% of them were migrating in the same Guangdong province. Except for mental health, other health statuses among migrants had significant differences compared with local registered population, e.g. self-reported health was better, but subjective well-being was worse. However, these health measurements were improved with more years of residence. Moreover, our results show that two aspects of social integration, economic integration and self-identity, were significantly associated with health status. Subjective feeling of relative social status levels were more associated with health, which prompted the attention to social fairness and the creation of a fair and respectful culture. More interventions could be experimented, such as encouraging internal migrants to participate in community activities more actively, educating local registered residents to treat internal migrants more equally, and developing self-identity among internal migrants. Better social, economic, and cultural environment can benefit internal migrants’ health statuses.
PMCID: PMC4749174  PMID: 26863008
11.  Effects of Osseointegration by Bone Morphogenetic Protein-2 on Titanium Implants In Vitro and In Vivo 
This study designed a biomimetic implant for reducing healing time and achieving early osseointegration to create an active surface. Bone morphogenetic protein-2 (BMP-2) is a strong regulator protein in osteogenic pathways. Due to hardly maintaining BMP-2 biological function and specificity, BMP-2 efficient delivery on implant surfaces is the main challenge for the clinic application. In this study, a novel method for synthesizing functionalized silane film for superior modification with BMP-2 on titanium surfaces is proposed. Three groups were compared with and without BMP-2 on modified titanium surfaces in vitro and in vivo: mechanical grinding; electrochemical modification through potentiostatic anodization (ECH); and sandblasting, alkali heating, and etching (SMART). Cell tests indicated that the ECH and SMART groups with BMP-2 markedly promoted D1 cell activity and differentiation compared with the groups without BMP-2. Moreover, the SMART group with a BMP-2 surface markedly promoted early alkaline phosphatase expression in the D1 cells compared with the other surface groups. Compared with these groups in vivo, SMART silaning with BMP-2 showed superior bone quality and created contact areas between implant and surrounding bones. The SMART group with BMP-2 could promote cell mineralization in vitro and osseointegration in vivo, indicating potential clinical use.
PMCID: PMC4761669  PMID: 26977141
12.  Additional Primary Malignancies in Patients with Gastrointestinal Stromal Tumor (GIST): A Clinicopathologic Study of 260 Patients with Molecular Analysis and Review of the Literature 
Annals of surgical oncology  2015;22(8):2633-2639.
The incidence of other primary neoplasms in gastrointestinal stromal tumor (GIST) patients is relatively high. Our aim was to better characterize the clinicopathologic and molecular relationships in a cohort of GIST patients.
All GIST patients with tumor samples sent for molecular testing were identified via electronic medical records. Clinicopathologic characteristics of GIST and additional primary malignancies were analyzed.
Of 260 patients, 50 (19 %) had at least one additional primary malignancy. In 33 patients, separate primary neoplasms predated their GIST diagnosis and most commonly included: prostate (n = 9), breast (n = 8), and hematologic (n = 5). Renal (n = 4) and hematologic (n = 3) malignancies were the most frequent cancers identified after GIST diagnosis. The majority (8 of 12, 66 %) of malignancies diagnosed after GIST were found incidentally. Patients who developed other malignancies after GIST more often had KIT exon 11 mutations (100 vs. 66 %, P = 0.01). In comparison to patients with only GIST, patients with a second primary neoplasm of any chronology had GISTs with increased mitotic rate (≥5 per 50 high-power fields) (P = 0.0006). Literature review revealed colorectal cancer, gastric, prostate, renal, leukemia, and desmoid-type fibromatosis as the most common secondary neoplasms.
Nineteen percent of GIST patients develop other malignancies. This is the first report to describe a relationship between additional primary malignancy and both mutation and mitotic rate of GIST. Although the basis of these relationships remains to be investigated, caution in the clinical management of GIST patients with additional lesions is warranted.
PMCID: PMC4508237  PMID: 25564173
13.  An International Multicenter Study Assessing the Role of Ethnicity on Variation of Lumbar Facet Joint Orientation and the Occurrence of Degenerative Spondylolisthesis in Asia Pacific: A Study from the AOSpine Asia Pacific Research Collaboration Consortium 
Global Spine Journal  2015;6(1):35-45.
Study Design A multinational, multiethnic, cross-sectional image-based study was performed in 33 institutions, representing 10 countries, which were part of the AOSpine Asia Pacific Research Collaboration Consortium.
Objective Lumbar facet joint orientation has been reported to be associated with the development of degenerative spondylolisthesis (DS). The role of ethnicity regarding facet joint orientation remains uncertain. As such, the following study was performed across a wide-ranging population base to assess the role of ethnicity in facet joint orientation in patients with DS in the Asia Pacific region.
Methods Lateral standing X-rays and axial magnetic resonance imaging scans were obtained for patients with lumbar DS. The DS parameters and facet joint angulations were assessed from L3–S1. Sex, age, body mass index (BMI), and ethnicity were also noted.
Results The study included 371 patients with known ethnic origin (mean age: 62.0 years; 64% males, 36% females). The mean BMI was 25.6 kg/m2. The level of DS was most prevalent at L4–L5 (74.7%). There were 28.8% Indian, 28.6% Japanese, 18.1% Chinese, 8.6% Korean, 6.5% Thai, 4.9% Caucasian, 2.7% Filipino, and 1.9% Malay patients. Variations in facet joint angulations were noted from L3 to S1 and between patients with and without DS (p < 0.05). No differences were noted with regards to sex and overall BMI to facet joint angulations (p > 0.05); however, increasing age was found to increase the degree of angulation throughout the lumbar spine (p < 0.05). Accounting for age and the presence or absence of DS at each level, no statistically significant differences between ethnicity and degree of facet joint angulations from L3–L5 were noted (p > 0.05). Ethnic variations were noted in non-DS L5–S1 facet joint angulations, predominantly between Caucasian, Chinese, and Indian ethnicities (p < 0.05).
Conclusions This study is the first to suggest that ethnicity may not play a role in facet joint orientation in the majority of cases of DS in the Asia-Pacific region. Findings from this study may facilitate future comparative studies in other multiethnic populations. An understanding of ethnic variability may assist in identifying those patients at risk of postsurgical development or progression of DS. This study also serves as a model for large-scale multicenter studies across different ethnic groups and cultural boundaries in Asia.
PMCID: PMC4733370  PMID: 26835200
degenerative; spondylolisthesis; facet; joints; morphology; ethnicity; Asia; AOSpine
14.  High Performance Transparent Transistor Memory Devices Using Nano-Floating Gate of Polymer/ZnO Nanocomposites 
Scientific Reports  2016;6:20129.
Nano-floating gate memory devices (NFGM) using metal nanoparticles (NPs) covered with an insulating polymer have been considered as a promising electronic device for the next-generation nonvolatile organic memory applications NPs. However, the transparency of the device with metal NPs is restricted to 60~70% due to the light absorption in the visible region caused by the surface plasmon resonance effects of metal NPs. To address this issue, we demonstrate a novel NFGM using the blends of hole-trapping poly (9-(4-vinylphenyl) carbazole) (PVPK) and electron-trapping ZnO NPs as the charge storage element. The memory devices exhibited a remarkably programmable memory window up to 60 V during the program/erase operations, which was attributed to the trapping/detrapping of charge carriers in ZnO NPs/PVPK composite. Furthermore, the devices showed the long-term retention time (>105 s) and WRER test (>200 cycles), indicating excellent electrical reliability and stability. Additionally, the fabricated transistor memory devices exhibited a relatively high transparency of 90% at the wavelength of 500 nm based on the spray-coated PEDOT:PSS as electrode, suggesting high potential for transparent organic electronic memory devices.
PMCID: PMC4735596  PMID: 26831222
15.  Association between C-reactive protein, incident liver cancer and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: a nested case-control study 
C-reactive protein is a marker of systemic inflammation that has been associated with the incidence and prognosis for a number of different cancers. Recent data suggests that C-reactive protein may be a prognostic factor for liver cancer and cirrhosis. However, few long-term studies are available.
We prospectively examined associations between serum C-reactive protein and subsequent risk of liver cancer incidence or chronic liver disease mortality in a nested case-control study performed in the Linxian Nutrition Intervention Trials cohort. Baseline serum C-reactive protein was measured for 220 incident liver cancer cases, 276 participants who died of chronic liver disease, and 1018 age-, sex-, and trial-matched controls. Unconditional logistical regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI).
Compared to the lowest quartile, subjects in the fourth quartile of serum C-reactive protein had a higher risk of liver cancer incidence (OR=1.63, 95% CI: 1.06–2.51), with a significant p-trend across quartiles (P=0.01). The association with liver cancer was only significant among men (Q4 vs Q1, OR=2.00, 1.10–3.62), but not among women (Q4 vs Q1, OR=1.15, 0.60–2.22). For chronic liver disease deaths, the corresponding risk estimate in men and women was 2.95(1.90–4.57), with a monotonic trend (P<0.001).
Higher serum C-reactive protein concentrations at baseline were associated with subsequent incidence of liver cancer and death from chronic liver disease.
Our findings suggest that levels of systemic inflammation may serve as a long-term marker of liver cancer and liver disease.
PMCID: PMC4323937  PMID: 25613115
C-reactive protein; Liver cancer; Chronic liver disease; Nested case-control study
16.  The role of PD-L1 in the radiation response and clinical outcome for bladder cancer 
Scientific Reports  2016;6:19740.
Identification of potential factors that can stratify a tumor’s response to specific therapies will aid in the selection of cancer therapy. The aim was to highlight the role of programmed cell death 1 ligand 1 (PD-L1) in bladder cancer. In this study, 92 of muscle-invasive bladder cancers and 28 of non- muscle invasive bladder cancers were selected for immunohistochemical staining analysis. Furthermore, human and murine bladder cancer cell lines were used to examine the correlation between PD-L1 and radiation response. Our data revealed that PD-L1 was overexpressed in the bladder tumor specimens compared with adjacent non-malignant specimens. Furthermore, the staining of PD-L1 was significantly linked to higher clinical stage, lower complete response rates and reduced disease-free survival rates. By in vitro and in vivo experiments, irradiation up-regulated the expression of PD-L1 in tumor cells, and its increase correlated with the irradiation dose. In immunocompetent mouse models, blocking PD-L1 induced a longer tumour growth delay following irradiation. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells was responsible to the effects of PD-L1 on radiation response. In conclusion, PD-L1 could be a significant clinical predictor for clinical stage and treatment response of bladder cancer.
PMCID: PMC4726250  PMID: 26804478
17.  Hybrid surgery for dural arteriovenous fistula in the neurosurgical hybrid operating suite 
BMJ Case Reports  2014;2014:bcr2013011060.
Treatment of a dural arteriovenous fistula (AVF), which is difficult to access by either the surgical or endovascular approach, is challenging. A hybrid technique, combining a microsurgical approach and endovascular embolization, can provide less invasive management of dural AVFs in a modern neurosurgical hybrid operating suite. We present a case of intracerebral hemorrhage in the left cerebellum secondary to dural AVF, Cognard type IV with numerous tiny feeders from the ascending pharyngeal artery branches. No adequate arterial or venous route for endovascular embolization was found by neuroangiography. The hybrid technique, combining keyhole pterional craniotomy and embolization with n-butyl cyanoacrylate glue injection via direct cannulation of the periclival venous plexus, succeeded in obliterating the dural AVF. Intraoperative angiography showed successful embolization of the dural AVF without any complication. This report illustrates the usefulness of the neurosurgical hybrid operating suite for the treatment of difficult dural AVFs.
PMCID: PMC3903304  PMID: 24459222
Technique; Intervention; Fistula
18.  Silver nanoparticles/chitosan oligosaccharide/poly(vinyl alcohol) nanofiber promotes wound healing by activating TGFβ1/Smad signaling pathway 
Wound healing occupies a remarkable place in everyday pathology and remains a challenging clinical problem. In our previous study, we prepared a silver nanoparticle/chitosan oligosaccharide/poly(vinyl alcohol) (PVA/COS-AgNPs) nanofiber via electrospinning and revealed that it could promote wound healing; however, the healing mechanism remained unknown. Therefore, we aimed to clarify the mechanism underlying the accelerated healing effect of the PVA/COS-AgNPs nanofiber. The TGFβ1/Smad signaling pathway is actively involved in wound healing. Considering the key role of this signaling pathway in wound healing, our preliminary study showed that the TGFβ1 level was significantly increased during the early stage of wound healing. Thus, in this study, hematoxylin–eosin, Masson’s trichrome, immunofluorescent staining, hydroxyproline content, quantitative real-time polymerase chain reaction, and Western blot analyses were used to analyze the wound healing in a rat model treated with gauze, the PVA/COS-AgNPs nanofiber, and the nanofiber plus SB431542 (an inhibitor of TGFβ1 receptor kinase). The results showed that the PVA/COS-AgNPs nanofiber promoted wound healing and upregulated the expression levels of cytokines associated with the TGFβ1/Smad signaling pathway such as TGFβ1, TGFβRI, TGFβRII, collagen I, collagen III, pSmad2, and pSmad3. Inhibiting this pathway with SB431542 resulted in prevention of the PVA/COS-AgNPs nanofiber-associated salutary effects on the early stage of wound healing and relative cytokines expression. In conclusion, the wound healing effect of the PVA/COS-AgNPs nanofiber involves activation of the TGFβ1/Smad signaling pathway.
PMCID: PMC4725631  PMID: 26855575
wound healing; electrospinning; nanofiber; silver nanoparticles; TGFβ1; Smad proteins
19.  Thermomechanical Behavior of Molded Metallic Glass Nanowires 
Scientific Reports  2016;6:19530.
Metallic glasses are disordered materials that offer the unique ability to perform thermoplastic forming operations at low thermal budget while preserving excellent mechanical properties such as high strength, large elastic strain limits, and wear resistance owing to the metallic nature of bonding and lack of internal defects. Interest in molding micro- and nanoscale metallic glass objects is driven by the promise of robust and high performance micro- and nanoelectromechanical systems and miniature energy conversion devices. Yet accurate and efficient processing of these materials hinges on a robust understanding of their thermomechanical behavior. Here, we combine large-scale thermoplastic tensile deformation of collections of Pt-based amorphous nanowires with quantitative thermomechanical studies of individual nanowires in creep-like conditions to demonstrate that superplastic-like flow persists to small length scales. Systematic studies as a function of temperature, strain-rate, and applied stress reveal the transition from Newtonian to non-Newtonian flow to be ubiquitous across the investigated length scales. However, we provide evidence that nanoscale specimens sustain greater free volume generation at elevated temperatures resulting in a flow transition at higher strain-rates than their bulk counterparts. Our results provide guidance for the design of thermoplastic processing methods and methods for verifying the flow response at the nanoscale.
PMCID: PMC4726219  PMID: 26787400
20.  Unplanned revision spinal surgery within a week: a retrospective analysis of surgical causes 
The need for revision surgery after a spinal surgery can cause a variety of problems, including reduced quality of life for the patient, additional medical expenses, and patient-physician conflicts. The purpose of this study was to evaluate the causes of unplanned revision spinal surgery within a week after the initial surgery in order to identify the surgical issues most commonly associated with unplanned revision surgery.
We retrospectively reviewed the medical records of all patients at who received a spinal surgery at a regional medical center from July 2004 to April 2011 in order to identify those who required a revision surgery within one week of their initial surgery. Patients were excluded if they received a vertebroplasty, kyphoplasty, or nerve block surgery, because those surgeries are one-day surgeries that do not require hospital admission. In addition, patients with a primary diagnosis of wound infection were also excluded since reoperations for infection control can be expected.
The overall incidence of unplanned revision spinal surgery during the time period covered by this review was 1.12 % (116/10,350 patients). The most common surgical causes of reoperation were screw malposition (41 patients), symptomatic epidural hematoma (27 patients), and inadequate decompression (37 patients). Screw malposition was the most common complication, with an incidence rate of 0.82 %. Screw instrumentation was significantly associated with revision surgery (p = 0.023), which suggests that this procedure carried a greater risk of requiring revision. The mean time interval to reoperation for epidural hematomas was significantly shorter than the intervals for other causes of revision spinal surgery (p < 0.001), which suggests that epidural hematoma was more emergent than other complications. Also, 25.93 % of patients who underwent hematoma removal experienced residual sequelae; this percentage was significantly higher than for other surgical causes of revision spinal surgery (p = 0.013).
The results suggest that to avoid the need for reoperation, screw malposition, inadequate decompression, and epidural hematoma are the key surgical complications to be guarded against. Accordingly, adequate decompression, epidural hematoma prevention, and proper pedicle screw placement may help reduce the incidence of revision surgery.
PMCID: PMC4714439  PMID: 26772974
Revision spinal surgery; Epidural hematoma; Inadequate decompression; Screw malposition; Posterior instrumentation
21.  The fusion rate of demineralized bone matrix compared with autogenous iliac bone graft for long multi-segment posterolateral spinal fusion 
Although autogenous iliac bone graft (AIBG) remains the gold standard for spine fusion, harvesting morbidity has prompted the search for alternatives especially for multi-segment fusion. This study aimed to evaluate the efficacy of using demineralized bone matrix (DBM) as a substitute of AIBG for long instrumented posterolateral fusion (≧ three-level fusion).
A total of 47 consecutive patients underwent laminectomy decompression, and multi-level instrumented posterolateral fusions were reviewed. Group 1 comprised 26 patients having DBM with autologous laminectomy bone (ALB). Group 2 consisted of 21 patients having AIBG with ALB. The fusion success evaluation was based on findings using the 12-month anteroposterior and dynamic plain radiographs.
Gender, age, and the number of fusion levels were similar for both groups. 21 of 26 (80.8 %) patients in group 1 and 18 of 21 (85.7 %) patients in group 2 were observed to achieve solid bony fusion. There was no statistical difference in the fusion success (p = 0.72). Blood loss was significantly more in group 2 (p = 0.02). The duration of the hospital stays and operative times being longer for group 2, but the difference was not significant.
DBM combined with ALB and osteoconductive materials is as effective as an autologous iliac bone graft with respect to long multi-segment posterolateral fusion success. DBM can be used as an effective bone graft substitute and may decrease morbidities associated with iliac bone graft harvest.
PMCID: PMC4700670  PMID: 26728876
Multi-segment posterolateral fusion; Demineralized bone matrix; Bone graft substitute; Autogenous iliac bone graft; Osteoconduction; Osteoinduction; Osteogenesis
22.  Pharmacological inhibition of TGFβ receptor improves Nkx2.5 cardiomyoblast-mediated regeneration 
Cardiovascular Research  2014;105(1):44-54.
Our previous study found that A83-01, a small molecule type 1 TGFβ receptor inhibitor, could induce proliferation of postnatal Nkx2.5+ cardiomyoblasts in vitro and enhance their cardiomyogenic differentiation. The present study addresses whether A83-01 treatment in vivo could increase cardiomyogenesis and improve cardiac function after myocardial infarction through an Nkx2.5+ cardiomyoblast-dependent process.
Methods and results
To determine the effect of A83-01 on the number of Nkx2.5+ cardiomyoblasts in the heart after myocardial injury, we treated transgenic Nkx2.5 enhancer-GFP reporter mice for 7 days with either A83-01 or DMSO and measured the number of GFP+ cardiomyoblasts in the heart at 1 week after injury by flow cytometry. To determine the degree of new cardiomyocyte formation after myocardial injury and the effect of A83-01 in this process, we employed inducible Nkx2.5 enhancer-Cre transgenic mice to lineage label postnatal Nkx2.5+ cardiomyoblasts and their differentiated progenies after myocardial injury. We also examined the cardiac function of each animal by intracardiac haemodynamic measurements. We found that A83-01 treatment significantly increased the number of Nkx2.5+ cardiomyoblasts at baseline and after myocardial injury, resulting in an increase in newly formed cardiomyocytes. Finally, we showed that A83-01 treatment significantly improved ventricular elastance and stroke work, leading to improved contractility after injury.
Pharmacological inhibition of TGFβ signalling improved cardiac function in injured mice and promoted the expansion and cardiomyogenic differentiation of Nkx2.5+ cardiomyoblasts. Direct modulation of resident cardiomyoblasts in vivo may be a promising strategy to enhance therapeutic cardiac regeneration.
PMCID: PMC4342671  PMID: 25362681
Nkx2.5; Cardiomyoblast; TGFβ; Regeneration; Myocardial infarction
23.  Incidence and survival of non-small cell lung cancer in Shanghai: a population-based cohort study 
BMJ Open  2015;5(12):e009419.
Large population-based studies on the incidence and outcome of non-small cell lung cancer (NSCLC) are lacking in mainland China. This study aimed to investigate the NSCLC incidence, demographic features and survival as well as factors affecting survival of patients with NSCLC in Shanghai.
Prospective observational cohort study.
Baseline information was collected from Shanghai Health Information Network, which is based on the Health Information Systems from all the comprehensive hospitals and specialist hospitals qualified for cancer diagnosis in the Shanghai metropolitan area.
All NSCLC cases identified from the database between 2011 and 2013 were recruited (15 020 patients).
Main results
The crude and age-adjusted incidences of NSCLC were 54.20 per 100 000 people (55.90 per 100 000 for men, 52.39 per 100 000 for women) and 39.05 per 100 000 people (41.43 per 100 000 for men and 37.13 per 100 000 for women), respectively. The median survival time was 22.7 months (95% CI 21.8 to 24.2 months) with an overall 1-year survival rate of 71.8% (95% CI 69.8% to 73.8%). The 1-year survival rate was 96.5% (95% CI 94.0% to 98.6%) in patients with stage I NSCLC, 89.1% (95% CI 83.3% to 94.9%) in patients with stage II NSCLC, 78.8% (95% CI 74.1% to 83.5%) in patients with stage IIIa NSCLC and 58.9% (95% CI 56.1% to 61.7%) in patients with stage IIIb/IV NSCLC. Multivariate analysis showed surgical resection (HR=0.607, 95% CI 0.511 to 0.722) and chemotherapy (HR=0.838, 95% CI 0.709 to 0.991) significantly improved survival. Factors associated with poor survival included older age, male sex, larger tumour size, lymph node metastasis, distant metastasis and squamous cell carcinoma.
A higher incidence and better survival rates for patients with NSCLC were identified when compared with previously published studies, which may provide evidence on the incidence and survival of NSCLC in China.
PMCID: PMC4691760  PMID: 26700282
24.  Danhong Huayu Koufuye combined with metformin attenuated diabetic retinopathy in Zucker diabetic fatty rats 
To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type-2 diabetes, and then to investigate the mechanisms.
ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed.
DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin.
DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism.
PMCID: PMC4651870  PMID: 26682154
diabetic retinopathy; Danhong Huayu Koufuye; metformin; Zucker diabetic fatty rat; antihyperglycemic activity; oxidative stress
25.  Full controlling of Fano resonances in metal-slit superlattice 
Scientific Reports  2015;5:18461.
Controlling of the lineshape of Fano resonance attracts much attention recently due to its wide capabilities for lasing, biosensing, slow-light applications and so on. However, the controllable Fano resonance always requires stringent alignment of complex symmetry-breaking structures and thus the manipulation could only be performed with limited degrees of freedom and narrow tuning range. Furthermore, there is no report so far on independent controlling of both the bright and dark modes in a single structure. Here, we semi-analytically show that the spectral position and linewidth of both the bright and dark modes can be tuned independently and/or simultaneously in a simple and symmetric metal-slit superlattice, and thus allowing for a free and continuous controlling of the lineshape of both the single and multiple Fano resonances. The independent controlling scheme is applicable for an extremely large electromagnetic spectrum range from optical to microwave frequencies, which is demonstrated by the numerical simulations with real metal and a microwave experiment. Our findings may provide convenient and flexible strategies for future tunable electromagnetic devices.
PMCID: PMC4683451  PMID: 26680258

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