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1.  The epidemiology, antifungal use and risk factors of death in elderly patients with candidemia: a multicentre retrospective study 
BMC Infectious Diseases  2014;14(1):609.
Background
The elderly patients affected by candidemia are growing in proportion to inpatients, but available data are limited. We aimed to determine the epidemiology, antifungal management and clinical risk factors of death in the elderly population with candidemia in China.
Methods
This retrospective study included 63 elderly (≥65 years) and 84 younger patients (16–60 years) at 4 tertiary hospitals. Multivariable logistic regression model was used to identify independent risk factors of death in elderly patients.
Results
The distribution of Candida species did not differ between elderly and younger patients (p >0.05). Resistance to fluconazole and voriconazole for non-Candida albicans species in elderly patients was approximately double that in younger patients. Host-related risk factors (e.g., underlying solid tumour, diabetes mellitus and chronic renal failure) and hospital-related factors (e.g., prior stay in an intensive care unit, mechanical ventilation, central vascular and urethral catheters placement) were identified more common in elderly patients. Elderly patients less often received triazoles and were less likely to receive antifungal therapies mostly because elderly or their guardians quit antifungal therapies. APACHE II scores and 30-day mortality were higher for elderly than younger patients (31.7% vs. 16.7%, p =0.032). For elderly patients, antifungal therapy administered before microbiological documentation was the only protective factor for death, whereas absence of antifungal therapies, receipt of mechanical ventilation and APACHE II score ≥20 were independent predictors of death.
Conclusions
Elderly patients with candidemia had poor prognoses characterized by certain host and hospital-related risk factors and special pathogen resistance features. More awareness of the burden of this disease is required, and the absence of antifungal therapies should be avoided to improve the prognoses of elderly patients with this severe infection.
doi:10.1186/s12879-014-0609-x
PMCID: PMC4247620  PMID: 25420435
Candidemia; Elderly; Antifungal agent; Risk factors; Death
2.  Prognostic significance of high-risk human papillomavirus and p16INK4A in patients with esophageal squamous cell carcinoma 
The prognostic value of the HPV status in ESCC is much controversial, this study aimed to determine the prognostic importance of high-risk HPV and p16 in patients with ESCC. A total of 105 consecutive patients who underwent esophagectomy in 2008 were included in this study. All specimens with ESCC were tested by in situ hybridization for HPV16/18 and immunohistochemistry for p16 expression. Kappa values were calculated using Cohen’s kappa test. The 5-year overall survival (OS) and progression-free survival (PFS) were calculated in relation to the two markers and the Cox proportional hazards model was used to determine the hazard ratio (HR) of variables. Thirty-nine (37.1%) of 105 were p16-positive, and HPV was detected in 29 of the 105 patients (27.6%) with ESCC. P16 was detected in 25 of the 29 patients (86.2%) who were HPV-positive, and only 14 of 76 patients (18.4%) who were HPV-negative (P < 0.001). Cohen’s kappa coefficient revealed an agreement in two researchers (kappa = 0.61). The 5-year OS rate and PFS rate in the p16-positive group were 64.1% and 58.7%, respectively, and the rates in the p16-negative group were 45.5%, 37.9%, respectively. The difference of survival rate between the two groups remained statistically significant. P16-positive patients had better 5-year rates of OS and PFS than p16-negative group (P = 0.02 and P = 0.007 by the Log-rank test, respectively). Using HPV status as a stratification factor, we found differences in OS and PFS that were consistent with those based on p16 expression. P16 is a very good marker of HPV infection for ESCC. HPV-positive or p16-positive ESCC is a distinct entity with a favorable prognosis compared with HPV-negative or p16-negative ESCC.
PMCID: PMC4238498  PMID: 25419379
Human papillomavirus; p16INK4A; squamous cell carcinoma; esophageal cancer; prognosis
3.  Expression of Angiogenesis Regulatory Proteins and Epithelial-Mesenchymal Transition Factors in Platelets of the Breast Cancer Patients 
The Scientific World Journal  2014;2014:878209.
Platelets play a role in tumor angiogenesis and growth and are the main transporters of several angiogenesis regulators. Here, we aimed to determine the levels of angiogenesis regulators and epithelial-mesenchymal transition factors sequestered by circulating platelets in breast cancer patients and age-matched healthy controls. Platelet pellets (PP) and platelet-poor plasma (PPP) were collected by routine protocols. Vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), thrombospondin-1 (TSP-1), platelet factor 4 (PF4), and transforming growth factor-β1 (TGF-β1) were measured by enzyme-linked immunosorbent assay. Angiogenesis-associated expression of VEGF (2.1 pg/106 platelets versus 0.9 pg/106 platelets, P < 0.001), PF4 (21.2 ng/106 platelets versus 10.2 ng/106 platelets, P < 0.001), PDGF-BB (42.9 pg/106 platelets versus 19.1 pg/106 platelets, P < 0.001), and TGF-β1 (15.3 ng/106 platelets versus 4.3 ng/106 platelets, P < 0.001) differed in the PP samples of cancer and control subjects. In addition, protein concentrations were associated with clinical characteristics (P < 0.05). Circulating platelets in breast cancer sequester higher levels of PF4, VEGF, PDGF-BB, and TGF-β1, suggesting a possible target for early diagnosis. VEGF, PDGF, and TGF-β1 concentrations in platelets may be associated with prognosis.
doi:10.1155/2014/878209
PMCID: PMC4212629  PMID: 25379550
4.  Effect of cycloxygenase-2 silencing on the malignant biological behavior of MCF-7 breast cancer cells 
Oncology Letters  2014;8(4):1628-1634.
The aim of the present study was to investigate the effect of cyclooxygenase-2 (COX-2) silencing on the malignant biological behavior of MCF-7 breast cancer cells. COX-2 short hairpin RNA (shRNA) and unassociated sequences were synthesized and a shRNA lentiviral vector was constructed. The vector was transfected into MCF-7 breast cancer cells, in which clones with stable expression were screened out. The expression of COX-2 mRNA and protein was silenced using RNA interference (RNAi). Quantitative polymerase chain reaction, western blotting, a mononuclear cell direct cytotoxicity assay (MTT assay), a cell invasion assay and scratch tests were performed to investigate the downregulation of COX-2 mRNA and protein expression, the proliferative activity and growth rate of MCF-7 breast cancer cells, the glioblastoma multiforme (GBM) penetrating capacity, the cell movement and migratory capacity, and vascular endothelial growth factor (VEGF)-A and VEGF-C protein expression. The results revealed that the sequence-specific shRNA significantly downregulated the expression of COX-2 at the mRNA and protein levels. Furthermore, the downregulation of COX-2 expression markedly decreased the invasive and metastatic capacities of the cells, suppressed the proliferation, decreased the rate of growth, decreased the capacity of GBM penetration and migration, and decreased the protein expression of VEGF-A and VEGF-C, the two key factors that regulate tumor angiogenesis and lymphangiogenesis. In conclusion, the RNAi technique effectively silenced COX-2 gene expression and inhibited MCF-7 breast cancer cell proliferation, invasion and metastasis by decreasing VEGF-A and VEGF-C expression, which regulates tumor angiogenesis and lymphangiogenesis. Therefore, an RNAi technique that targets COX-2 presents a promising prospect for breast cancer gene therapy.
doi:10.3892/ol.2014.2395
PMCID: PMC4156213  PMID: 25202381
RNA interference; cyclooxygenase-2; breast cancer; proliferation; invasion
5.  Integrated Parallel Reception, Excitation, and Shimming (iPRES) 
Purpose
To develop a new concept for a hardware platform that enables integrated parallel reception, excitation, and shimming (iPRES).
Theory
This concept uses a single coil array rather than separate arrays for parallel excitation/reception and B0 shimming. It relies on a novel design that allows a radiofrequency current (for excitation/reception) and a direct current (for B0 shimming) to coexist independently in the same coil.
Methods
Proof-of-concept B0 shimming experiments were performed with a two-coil array in a phantom, whereas B0 shimming simulations were performed with a 48-coil array in the human brain.
Results
Our experiments show that individually optimized direct currents applied in each coil can reduce the B0 root-mean-square error by 62–81% and minimize distortions in echo-planar images. The simulations show that dynamic shimming with the 48-coil iPRES array can reduce the B0 root-mean-square error in the prefrontal and temporal regions by 66–79% as compared to static 2nd-order spherical harmonic shimming and by 12–23% as compared to dynamic shimming with a 48-coil conventional shim array.
Conclusion
Our results demonstrate the feasibility of the iPRES concept to perform parallel excitation/reception and B0 shimming with a unified coil system as well as its promise for in vivo applications.
doi:10.1002/mrm.24766
PMCID: PMC3800110  PMID: 23629974
Parallel; excitation; reception; shimming; coil array
6.  Identifying species of moths (Lepidoptera) from Baihua Mountain, Beijing, China, using DNA barcodes 
Ecology and Evolution  2014;4(12):2472-2487.
DNA barcoding has become a promising means for the identification of organisms of all life-history stages. Currently, distance-based and tree-based methods are most widely used to define species boundaries and uncover cryptic species. However, there is no universal threshold of genetic distance values that can be used to distinguish taxonomic groups. Alternatively, DNA barcoding can deploy a “character-based” method, whereby species are identified through the discrete nucleotide substitutions. Our research focuses on the delimitation of moth species using DNA-barcoding methods. We analyzed 393 Lepidopteran specimens belonging to 80 morphologically recognized species with a standard cytochrome c oxidase subunit I (COI) sequencing approach, and deployed tree-based, distance-based, and diagnostic character-based methods to identify the taxa. The tree-based method divided the 393 specimens into 79 taxa (species), and the distance-based method divided them into 84 taxa (species). Although the diagnostic character-based method found only 39 so-identifiable species in the 80 species, with a reduction in sample size the accuracy rate substantially improved. For example, in the Arctiidae subset, all 12 species had diagnostics characteristics. Compared with traditional morphological method, molecular taxonomy performed well. All three methods enable the rapid delimitation of species, although they have different characteristics and different strengths. The tree-based and distance-based methods can be used for accurate species identification and biodiversity studies in large data sets, while the character-based method performs well in small data sets and can also be used as the foundation of species-specific biochips.
doi:10.1002/ece3.1110
PMCID: PMC4203292  PMID: 25360280
Bayesian; cytochrome c oxidase subunit I; diagnostic character; DNA barcode; genetic distance; Lepidoptera; maximum likelihood; moths; neighbor joining
7.  Association of Cyclin D and Estrogen Receptor α36 with Hepatocellular Adenomas of Female Mice under Chronic Endoplasmic Reticulum Stress 
Background & Aims
Hepatocellular adenomas (HCA) are benign tumors that can lead to medical complications. Chronic inflammation and mutations in β-catenin, HNF1α or GP130 are potential causes for human HCA. However, additional causes may exist due to heterogeneity of HCA. We investigated whether HCA are caused by endoplasmic reticulum (ER) stress.
Methods
Mice with a liver specific deletion of the major chaperone BiP (LGKO) were used. Liver tumor occurrence was examined in LGKO with or without feeding of a high fat diet (HFD) and characterized with immunohistochemistry with molecular markers of proliferation/malignancy. Molecular changes were analyzed with immunoblotting.
Results
Spontaneous monoclonal liver tumors were observed in 34% of LGKO females with constitutive hepatic ER stress. Lack of portal tracks or central veins, dilated sinusoidal spaces, hemorrhagic areas, active proliferation and Lipid deposits were observed in the liver tumors. HFD feeding induced multi-clonal liver tumors in 83% of the LGKO females versus zero in wild type females. Hepatocytes reactive to anti-glypican-3 antibodies were detected in the HFD-induced but not spontaneous tumors. In the liver tumors, inhibition of cyclin D and increase of the 36kD estrogen receptor variant (ERα36), active ATF4/6, GSK3β and ERK1/2 were detected whereas no change of HNF1α, β-catenin, p-53, androgen receptor α or estrogen receptor α was detected. HFD activated JAK and STAT3.
Conclusions
Our evidence supports a possible link of HCA with ER stress and altered expression of cyclin D and ERα36. Additional stress such as HFD may promote malignant transformation of HCA through the JAK-STAT pathway.
doi:10.1111/jgh.12084
PMCID: PMC3584191  PMID: 23216077
metabolic stress; unfolded protein response (UPR); high fat diet (HFD); abnormal function of cyclin D; sex hormone receptor variants; hepatocellular tumorigenesis
8.  Radical cystectomy for bladder cancer: oncologic outcome in 271 Chinese patients 
Chinese Journal of Cancer  2014;33(3):165-171.
Few large scale studies have reported the oncologic outcome of radical cystectomy for treating bladder cancer in China; hence, we lack long-term prognostic information. The aim of the current study was to determine the survival rate and prognostic factors of patients who underwent radical cystectomy for bladder cancer in a Chinese medical center. We retrospectively analyzed clinicopathologic data from 271 bladder cancer patients who underwent radical cystectomy between 2000 and 2011. Univariate and multivariate analyses were conducted to identify independent prognostic predictors for this cohort. Median follow-up was 31.7 months (range, 0.2–139.1 months). Thirty-day mortality was (1.4%). The 5-year recurrence-free survival, cancer-specific survival (CSS), and overall survival rates were 61.6%, 72.9%, and 68.0%, respectively. The 5-year CSS rates of patients with T1–T4 disease were 90.7%, 85.0%, 51.0%, and 18.0%, respectively. Patients with organ-confined disease had a higher 5-year CSS rate than those with extravesical disease (81.4% vs. 34.9%, P < 0.001). For the 38 patients (14%) with lymph node involvement, the 5-year CSS rate was 27.7%—significantly lower than that of patients without lymph node metastasis (P < 0.001). The 5-year CSS rate was much higher in patients with low grade tumor than in those with high grade tumor (98.1% vs. 68.1%, P < 0.001). Multivariate Cox regression showed that patient age (hazard ratio, 2.045; P = 0.013) and T category (hazard ratio, 2.213; P < 0.001) were independent predictors for CSS. These results suggest that radical cystectomy is a safe and effective method for treating bladder cancer in Chinese patients. Old age and high T category were associated with poor prognosis in bladder cancer patients who underwent radical cystectomy.
doi:10.5732/cjc.012.10312
PMCID: PMC3966145  PMID: 23958053
Bladder cancer; radical cystectomy; prognosis
9.  HPV Infection in Esophageal Squamous Cell Carcinoma and Its Relationship to the Prognosis of Patients in Northern China 
The Scientific World Journal  2014;2014:804738.
Purpose. Human papillomavirus (HPV) as a risk factor for esophageal squamous cell carcinoma (ESCC) has previously been studied, but importance of HPV status in ESCC for prognosis is less clear. Methods. A total of 105 specimens with ESCC were tested by in situ hybridization for HPV 16/18 and immunohistochemistry for p16 expression. The 5-year overall survival (OS) and progression-free survival were calculated in relation to these markers and the Cox proportional hazards model was used to determine the hazard ratio (HR) of variables in univariate and multivariate analysis. Results. HPV was detected in 27.6% (29) of the 105 patients with ESCC, and all positive cases were HPV-16. Twenty-five (86.2%) of the 29 HPV-positive tumors were stained positive for p16. HPV infected patients had better 5-year rates of OS (65.9% versus 43.4% among patients with HPV-negative tumors; P = 0.002 by the log-rank test) and had a 63% reduction in the risk of death (adjusted HR = 0.37, 95% CI = 0.16 to 0.82, and P = 0.01). Conclusions. HPV infection may be one of many factors contributing to the development of ESCC and tumor HPV status is an independent prognostic factor for survival among patients with ESCC.
doi:10.1155/2014/804738
PMCID: PMC3914373  PMID: 24558329
10.  Anatomical retroperitoneoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell tumors: Initial operative experience 
Asian Journal of Andrology  2013;16(1):136-139.
To introduce the technique of anatomical retroperitoneoscopic retroperitoneal lymph node dissection (ARRPLND) was performed in 12 consecutive patients with a clinical stage I nonseminomatous germ-cell tumor (NSGCT) between February 2008 and October 2010. All procedures were performed using a modified template nerve-sparing approach. The retroperitoneal space was adequately expanded using double gasbags. After the retroperitoneal fat was cleared, two relatively bloodless planes were entered consecutively to expose the lymph node and permit dissection. Dissection proceeded first in the plane between the anterior renal fascia and posterior peritoneum, and secondly in the avascular plane between the posterior renal fascia and transversalis fascia. The proximal spermatic vein was clipped at the initial stage. En bloc resection of the lymph tissue and fat between the anterior renal fascia and posterior renal fascia were performed. Three patients (25%) had pathologic stage IIA disease and received adjuvant chemotherapy. No recurrence was observed during follow-up ranging from 26 to 58 months. The median operative time was 205 min (range: 165–430 min) and median estimated blood loss was 320 ml (range: 100–1200 ml). There were two intraoperative complications (Clavien grade II) and one open conversion due to perforation of the peritoneum. Postoperative complications (Clavien I) developed in three patients. Normal antegrade ejaculation recovered by 1 month following the operation. Our preliminary results indicate that ARRPLND is technically feasible and associated with satisfactory clinical outcomes for clinical stage I NSGCT. Further studies are necessary to evaluate this technique.
doi:10.4103/1008-682X.122188
PMCID: PMC3901872  PMID: 24369147
nonseminomatous; retroperitoneoscopic; retroperitoneal lymph node; testicular cancer
11.  Abnormal anxiety- and depression-like behaviors in mice lacking both central serotonergic neurons and pancreatic islet cells 
Dysfunction of central serotonin (5-HT) system has been proposed to be one of the underlying mechanisms for anxiety and depression, and the association of diabetes mellitus and psychiatric disorders has been noticed by the high prevalence of anxiety/depression in patients with diabetes mellitus. This promoted us to examine these behaviors in central 5-HT-deficient mice and those also suffering with diabetes mellitus. Mice lacking either 5-HT or central serotonergic neurons were generated by conditional deletion of Tph2 or Lmx1b respectively. Simultaneous depletion of both central serotonergic neurons and pancreatic islet cells was achieved by administration of diphtheria toxin (DT) in Pet1-Cre;Rosa26-DT receptor (DTR) mice. The central 5-HT-deficient mice showed reduced anxiety-like behaviors as they spent more time in and entered more often into the light box in the light/dark box test compared with controls; similar results were observed in the elevated plus maze test. However, they displayed no differences in the immobility time of the forced swimming and tail suspension tests suggesting normal depression-like behaviors in central 5-HT-deficient mice. As expected, DT-treated Pet1-Cre;Rosa26-DTR mice lacking both central serotonergic neurons and pancreatic islet endocrine cells exhibited several classic diabetic symptoms. Interestingly, they displayed increased anxiety-like behaviors but reduced immobility time in the forced swimming and tail suspension tests. Furthermore, the hippocampal neurogenesis was dramatically enhanced in these mice. These results suggest that the deficiency of central 5-HT may not be sufficient to induce anxiety/depression-like behaviors in mice, and the enhanced hippocampal neurogenesis may contribute to the altered depression-like behaviors in the 5-HT-deficient mice with diabetes. Our current investigation provides understanding the relationship between diabetes mellitus and psychiatric disorders.
doi:10.3389/fnbeh.2014.00325
PMCID: PMC4172023  PMID: 25294992
diabetes mellitus; anxiety; depression; serotonin; Pet1; adult neurogenesis
12.  A Case of Lead Poisoning due to a Mixture of Talisman Ash 
Background
Lead is a metal that has no biological function useful for the human body. In Korea, non-occupational exposure to lead has mostly occurred through taking oriental medicine. However, in this paper we report a case of lead poisoning caused by ingesting talisman material.
Case presentation
A 16-year-old male patient complained of severe abdominal pain after taking cinnabar, a talisman material. He was diagnosed with lead poisoning accompanied by acute hepatitis. We confirmed that the cinnabar the patient took contained about 10% elemental lead. After symptom management, the patients’ symptoms, liver function test results, and blood lead concentration level improved.
Conclusion
Lead poisoning can be accompanied by hepatitis, although rarely. As we have confirmed that cinnabar as a talisman material is harmful to the human body, measures to prevent its misuse are needed.
doi:10.1186/2052-4374-25-37
PMCID: PMC3923338  PMID: 24472628
Lead poisoning; Talisman; Cinnabar; Acute hepatitis
13.  Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent penile squamous cell carcinoma 
Chinese Journal of Cancer  2013;32(11):619-623.
The prognosis of locally advanced or recurrent squamous cell carcinoma (SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregionally advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overall survival for the patients was 24 months (range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in locoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.
doi:10.5732/cjc.012.10275
PMCID: PMC3845548  PMID: 23668929
Penile squamous cell carcinoma; intraarterial chemotherapy; gemcitabine; cisplatin
14.  The Association between Shift Work and the Metabolic Syndrome in Female Workers 
Objective
This study aimed to determine identify any association between shift work and the metabolic syndrome by comparing the prevalence rates of the metabolic syndrome in shift work groups and daytime work groups for female workers.
Methods
Based on data from health examinations carried out from April to December of 2012, we selected as our subjects 254 female workers from the Daegu area Dyeing Industrial Complex. We diagnosed the metabolic syndrome using the examination results, and information about age, whether or not they did shift work, job type, smoking habits, drinking habits, exercise habits, and past medical history was collected through self-administered questionnaire surveys and face-to-face interviews. The variables found in a univariate analysis to be significant in the occurrence of the metabolic syndrome - age, drinking habits, exercise habits, and shift work - were included in a logistic regression analysis of the risk of the metabolic syndrome for female workers.
Results
The prevalence rates of the metabolic syndrome for the total group of study subjects was 11.8%, for daytime workers was 2.8%, and for shift workers was 15.3%. A logistic regression analysis of the odds of the metabolic syndrome for female workers was conducted that included factors associated with the occurrence of the metabolic syndrome: age, drinking habits, exercise habits, and shift work. The results revealed that the odds ratio of the metabolic syndrome in the shift work group, 6.30 (95% CI 1.24-32.15), was significantly higher when compared with the daytime work group.
Conclusion
Shift work appears to have an association with the metabolic syndrome in female workers. Accordingly, we believe that the attention of government agencies and business owners is needed together with the individual practice of health behaviors to manage the metabolic syndrome for the prevention of cardiovascular disease in female shift workers.
doi:10.1186/2052-4374-25-33
PMCID: PMC3923341  PMID: 24472469
Shift work; Female workers; Metabolic syndrome
15.  Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors 
Frontiers in Genetics  2013;4:224.
Mortality from liver cancer in humans is increasingly attributable to heavy or long-term alcohol consumption. The mechanisms by which alcohol exerts its carcinogenic effect are not well understood. In this study, the role of alcohol-induced endoplasmic reticulum (ER) stress response in liver cancer development was investigated using an animal model with a liver knockout (KO) of the chaperone BiP and under constitutive hepatic ER stress. Long-term alcohol and high fat diet feeding resulted in higher levels of serum alanine aminotransferase, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months) KO females than in either middle-aged (6 months) KOs or older (aged 16 months) wild type females. In the older KO females, stronger effects of the alcohol on methylation of CpG islands at promoter regions of genes involved in the ER-associated degradation (ERAD) were also detected. Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with epidermal growth factor-like domains 2), Herpud1 (homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member), Wfs1 (Wolfram syndrome gene), and Yod1 (deubiquitinating enzyme 1) was co-present with decreased proteasome activities, increased estrogen receptor α variant (ERα36), and enhanced phosphorylations of ERK1/2 (extracellular signal-regulated protein kinases 1 and 2) and STAT3 (the signal transducers and activators of transcription) in the older KO female fed alcohol. Our results suggest that long-term alcohol consumption and aging may promote liver tumorigenesis in females through interfering with DNA methylation and expression of genes involved in the ERAD.
doi:10.3389/fgene.2013.00224
PMCID: PMC3813967  PMID: 24198826
alcohol; aging; unfolded protein response; ERAD; hepatocellular tumorigenesis
16.  A retrospective study: the prognostic value of anemia, smoking and drinking in esophageal squamous cell carcinoma with primary radiotherapy 
Background
Few studies have investigated the relationship between anemia, smoking, drinking and survival in esophageal squamous cell carcinoma (ESCC) with primary radiotherapy. This study had the aim of evaluating the prognostic value of anemia, smoking and drinking in patients receiving primary radiotherapy for ESCC.
Methods
A total of 79 patients who underwent radiotherapy during initial treatment for ESCC were included in this study. The 2-year overall survival (OS) and disease-free survival (DFS) were analyzed between the anemic and non-anemic groups, non-smokers and smokers, and non-drinkers and drinkers using the Kaplan-Meier method and the Cox proportional hazards model.
Results
There were 79 patients (10 male) of median age 63 (range 38 to 84) years. The 2-year OS and DFS were 36% and 25%, respectively, in the non-anemic group, and 17% and 13%, respectively, in the anemic group (P = 0.019 for OS; P = 0.029 for DFS) using the Kaplan-Meier method. Survival analysis using the Kaplan-Meier method showed that the 2-year OS and DFS had no statistical difference between smoking, drinking and survival. In a univariate analysis, anemia was identified as a significant prognostic factor for 2-year OS (hazard ratio (HR) = 1.897; P = 0.024) and 2-year DFS (HR = 1.776; P = 0.036), independent of tumor, lymph node, metastasis (TNM) stage. In a multivariate analysis, anemia was identified as a highly significant prognostic factor for 2-year OS (HR = 2.125; P = 0.011) and 2-year DFS (HR = 1.898; P = 0.025), independent of TNM stage and initial treatment. We found no statistical difference in the 2-year OS and DFS associated with smoking (P > 0.2) and drinking (P > 0.6) using univariate and multivariate analysis.
Conclusions
Smoking and drinking were not prognostic for 2-year OS or DFS. Anemia before radiotherapy was associated with poor prognosis and an increased risk of relapse, which may serve as a new prognostic characteristic in ESCC treated with primary radiotherapy. Hemoglobin is a routine examination and anemia is therefore simple and quick to determine.
doi:10.1186/1477-7819-11-249
PMCID: PMC3852102  PMID: 24083572
Anemia; Survival; Smoking; Drinking; Squamous cell carcinoma; Esophageal neoplasms
17.  Biomimetic enzyme nanocomplexes and their use as antidotes and preventive measures for alcohol intoxication 
Nature nanotechnology  2013;8(3):187-192.
Organisms have sophisticated subcellular compartments containing enzymes that function in tandem. These confined compartments ensure effective chemical transformation and transport of molecules, and the elimination of toxic metabolic wastes1,2. Creating functional enzyme complexes that are confined in a similar way remains challenging. Here we show that two or more enzymes with complementary functions can be assembled and encapsulated within a thin polymer shell to form enzyme nanocomplexes. These nanocomplexes exhibit improved catalytic efficiency and enhanced stability when compared with free enzymes. Furthermore, the co-localized enzymes display complementary functions, whereby toxic intermediates generated by one enzyme can be promptly eliminated by another enzyme. We show that nanocomplexes containing alcohol oxidase and catalase could reduce blood alcohol levels in intoxicated mice, offering an alternative antidote and prophylactic for alcohol intoxication.
doi:10.1038/nnano.2012.264
PMCID: PMC3670615  PMID: 23416793
18.  Complications of radical nephrectomy for renal cell carcinoma: a retrospective study comparing transperitoneal and retroperitoneal approaches using a standardized reporting methodology in two Chinese centers 
Chinese Journal of Cancer  2013;32(8):461-468.
The reporting of complications following transperitoneal and retroperitoneal open radical nephrectomy (RN) is nonstandardized. This study aimed to compare early complications between the two approaches using a standardized reporting methodology in a large contemporary cohort. Between 1996 and 2009, 558 patients underwent open RN for renal cell carcinoma (RCC) in our two centers (424 from Sun Yat-sen University Cancer Center and 134 from the First Affiliated Hospital of Sun Yat-sen University). Records were reviewed for clinicopathologic features and complications. Complications were graded using the Clavien system based on the severity of impact. One hundred and five patients (18.8%) had one or more early complications (168 complications overall). The overall rates of grades I to V complications were 5.6%, 10.8%, 2.2%, 0.4%, and 0.2%, respectively. Patients who underwent transperitoneal RN did not experience more overall or procedure-related complications than those who underwent retroperitoneal RN (P = 0.911 and P = 0.851, respectively). On subgroup analysis, neither grade I/II nor grades III-V complications were significantly different between the transperitonal RN and retroperitoneal RN groups. Multivariate analysis showed that for any grade of complication, age (P = 0.016) and estimated blood loss (P = 0.001) were significant predictors. We concluded that open RN is a safe procedure associated with low rates of serious morbidity and mortality. Compared with retroperitoneal RN, transperitoneal RN was not associated with more complications. Older patient and more blood loss at surgery were independent predictors for higher early postoperative complication rates.
doi:10.5732/cjc.012.10185
PMCID: PMC3845581  PMID: 23298461
Radical nephrectomy; complication; standardized reporting methodology
19.  Recurrence and histological evolution of dysembryoplastic neuroepithelial tumor: A case report and review of the literature 
Oncology Letters  2013;6(4):907-914.
Studies of recurrent dysembryoplastic neuroepithelial tumors (DNTs) are distinctly rare. The present study reports the case of a 15-year-old female with a temporal lobe DNT, which recurred and transformed into an astrocytoma (WHO grade II) five years after an initial gross total resection (GTR). Furthermore, all the previous studies on recurrent DNT are reviewed. Although the majority of DNT cases demonstrate benign behavior, recurrent DNTs have been observed following a GTR of the tumor. Patients do not appear to benefit from post-operative adjuvant therapy, and inappropriate radiotherapy or chemotherapy may result in tumor recurrence or malignant transformation. The prognosis is favorable if a GTR of the recurrent tumor is achieved. The use of regular imaging examinations and the maintenance of a long-term follow-up is of importance following a tumor resection.
doi:10.3892/ol.2013.1480
PMCID: PMC3796405  PMID: 24137435
dysembryoplastic neuroepithelial tumor; astrocytoma; recurrent; malignant transformation; prognosis
20.  Prevalence of hyperuricemia and its related risk factors in healthy adults from Northern and Northeastern Chinese provinces 
BMC Public Health  2013;13:664.
Background
Hyperuricemia (HUA) is a potential risk factor for developing insulin resistance, hypertension, dyslipidemia and cardiovascular disease. Therefore, we studied the prevalence of HUA and associated risk factors in the population of two provinces in northern China.
Methods
Based on the research of Chinese Physiological Constant and Health Conditions conducted in 2008–2010, we enrolled 29,639 subjects in a randomized, stratified study in four sampling areas in Heilongjiang Province and the Inner Mongolia Autonomous Region. We collected 13,140 serum samples to determine biochemical indicators including uric acid(UA), glucose, blood lipids, liver function, and renal function, and finally a representative sample of 8439 aged 18 years and older was determined. We also defined and stratified HUA, hypertension, diabetes, obesity and lipid abnormalities according to international guidelines.
Results
There were significant differences in the UA levels between different genders and regions. The total prevalence of HUA is 13.7%. Men had a higher prevalence of HUA than women (21% vs. 7.9%; P < 0.0001). As age increased, HUA prevalence decreased in men but rose in women. The suburbs of big cities had the highest HUA prevalence (18.7%), and in high-prevalence areas the proportion of women with HUA also increased. A stepwise logistic regression model was used to filter out twelve HUA risk factors, including age, gender, residence, hypercholesterolemia, hypertriglyceridemia, impaired fasting glucose, hypertension, obesity, abdominal obesity, CKD, drinking and sleeping. After adjusting for these factors, the odds ratio of HUA was 1.92 times higher in men than in women. Compared with agricultural and pastoral areas, the odds ratio of having HUA was 2.14 for participants in the suburbs of big cities and 1.57 in the center of big cities.
Conclusions
The prevalence of HUA is high in northern China. The differences in HUA prevalence by geographic region suggested that unbalanced economic development and health education, therefore HUA prevention measures should be strengthened to improve quality of life and reduce health care costs.
doi:10.1186/1471-2458-13-664
PMCID: PMC3722003  PMID: 23866159
Prevalence; Hyperuricemia; Risk factors
21.  Optimization of Pulse-Field Gel Electrophoresis for Subtyping of Klebsiella pneumoniae 
A total of 110 strains of Klebsiella pneumoniae were used to optimize pulsed-field gel electrophoresis (PFGE) for subtyping of K. pneumoniae. For optimization of electrophoresis parameters (EPs) of XbaI-PFGE, 11 isolates were analyzed with XbaI digestion using three EPs. The EP of a switch time of 6 to 36 s for 18.5 h gave clearest patterns and was declared the optimal EP for XbaI PFGE of K. pneumoniae. By software analysis and pilot study, AvrII was chosen as another PFGE enzyme. Both XbaI- and AvrII-PFGE gave D-values higher than 0.99 for 69 K. pneumoniae isolated from different sources. Our results also showed good typeability, reproducibility of both XbaI- and AvrII-PFGE for K. pneumoniae subtyping. Furthermore, the established PFGE method also had good discriminatory power to distinguish outbreak K. pneumoniae strains and a high degree of consistency with multilocus sequence typing method. A rapid PFGE protocol was established here, which could be used for genotyping and other researches of K. pneumoniae.
doi:10.3390/ijerph10072720
PMCID: PMC3734452  PMID: 23880721
Klebsiella pneumoniae; pulsed-field gel electrophoresis; molecular subtyping
22.  Serum γ-glutamyltransferase and uric acid levels are associated with impaired fasting glucose in adults from Inner Mongolia, China 
BMC Public Health  2013;13:294.
Background
Serum γ-glutamyltransferase (GGT) and uric acid (UA) levels are elevated in patients with diabetes or cardiovascular disease. Prediabetes, characterized by impaired glucose tolerance, is an important risk factor for overt diabetes as well as cardiovascular disease. Therefore, the aim of this study was to explore the relationship between GGT, UA and prediabetes in a Chinese population, and provide a scientific basis for the early prevention and treatment of diabetes.
Methods
We performed a cross-sectional population-based study in a cohort of 2694 subjects (1211 men and 1483 women, aged 35–86 years). Questionnaires and physical examinations were performed using standardized procedures. Fasting blood was collected to measure glucose and other biochemical parameters. The subjects were divided into two groups with either normal fasting glucose (NFG) or impaired fasting glucose (IFG), according to international diagnostic criteria. Logistic regression analysis was performed to estimate odds ratios (OR) and 95% confidence intervals.
Results
Compared with the NFG group, the IFG group had significantly higher blood pressure but lower high-density lipoprotein–cholesterol in women. Body mass index, waist circumference, triglyceride, glucose, GGT, and UA levels were significantly higher in males and females in the IFG group than those in the NFG group. Logistic regression analysis revealed that the OR for prediabetes increased with increasing serum GGT quartiles and UA quartiles. GGT and UA were positively associated with prediabetes in men and women, independent of age, ethnicity, smoking, alcohol consumption, blood pressure, physical labor, and other confounders.
Conclusions
We found that serum GGT and UA levels were positively associated with prediabetes in men and women living in areas inhabited by Chinese ethnic minorities. As elevated GGT and UA levels were associated with significantly increased risk of prediabetes, they may be used as sensitive biological markers of prediabetes.
doi:10.1186/1471-2458-13-294
PMCID: PMC3622625  PMID: 23552170
γ-Glutamyltransferase; Uric acid; Prediabetes; Impaired fasting glucose
23.  Renal plasmacytoma: Report of a rare case and review of the literature 
Oncology Letters  2013;5(6):1839-1843.
Renal plasmacytoma is extremely rare, presenting diagnostic challenges due to its unusual location and non-specific or absent symptoms. To the best of our knowledge, only 24 cases of renal plasmacytoma have been reported in the literature. The present study reports a case of primary renal plasmacytoma in a 46-year-old female patient. Computed tomography (CT) revealed that the mass was located in the lower pole of the left kidney and metastasis was detected in an enlarged para-aortic lymph node. Following careful preparation, a partial nephrectomy was performed and the retroperitoneal lymph node was resected. A pathological examination revealed a renal parenchyma with lymph node involvement; this was confirmed by immunohistochemistry and nested polymerase chain reaction (PCR). Consequently, a diagnosis of a renal extramedullary plasmacytoma (EMP) was proposed. Following this unexpected diagnosis, various examinations were performed, but there was no evidence of systemic plasma cell disease. The patient refused further therapy, including external beam radiotherapy and chemotherapy. Abdominal CT was performed three months post-surgery and did not reveal any relapse. The patient remains disease-free at nine months post-surgery. The current study also presents a review of the literature. Although the general prognosis and outcome of EMP is good, a follow-up examination is recommended due to the possibility of relapse or progression to plasma cell neoplasm (PCN).
doi:10.3892/ol.2013.1282
PMCID: PMC3700893  PMID: 23833652
extramedullary plasmacytoma; kidney; multiple myeloma
24.  Chronic Unpredictable Stress Decreases Expression of Brain-Derived Neurotrophic Factor (BDNF) in Mouse Ovaries: Relationship to Oocytes Developmental Potential 
PLoS ONE  2012;7(12):e52331.
Background
Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary.
Methods
Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA) axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated.
Results
Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn’t affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment.
Conclusion
BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress.
doi:10.1371/journal.pone.0052331
PMCID: PMC3527516  PMID: 23284991
25.  Urinary trypsin inhibitor attenuates lipopolysaccharide-induced neutrophil activation 
Korean Journal of Anesthesiology  2012;63(6):540-546.
Background
Urinary trypsin inhibitor (UTI), which is speculated to have anti-inflammatory effects, is one of serine protease inhibitors found in human urine and blood. The present study was conducted to clarify the effect of urinary trypsin inhibitor (UTI) on human neutrophil activation and its intracellular signaling mechanism in vitro.
Methods
To assess the possible interactions between UTI and lipopolysaccharide (LPS) in neutrophil activation, neutrophils from human blood were incubated with varying concentrations of UTI (1, 10, 100, 1,000 and 10,000 U/ml) plus LPS (100 ng/ml) or LPS alone in 24-well plates (5 × 106 cells/well). We measured protein levels for interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) using enzyme-linked immunosorbent assay (ELISA) kits after 4 hours of incubation period. To elucidate the intracellular signaling pathway, we also measured the levels of phosphorylation of p38, ERK1/2 and JNK via Western blot analysis. Moreover, the nuclear levels of nuclear factor-kappa B (NF-κB) were determined with electrophoretic mobility shift assays (EMSA).
Results
UTI decreased the expression of inflammatory cytokines, including TNF-α and IL-6, and activation of intracellular signaling pathways, such as JNK, but not P38, ERK1/2 and nuclear translocation of NF-κB.
Conclusions
UTI can attenuate LPS-induced neutrophil responses and may partially contribute to the treatment of neutrophil-mediated inflammatory diseases.
doi:10.4097/kjae.2012.63.6.540
PMCID: PMC3531534  PMID: 23277816
Cytokines; Mitogen activated protein kinases; Neutrophils; Urinary trypsin inhibitor

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