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1.  Burden of Disease Measured by Disability-Adjusted Life Years and a Disease Forecasting Time Series Model of Scrub Typhus in Laiwu, China 
Background
Laiwu District is recognized as a hyper-endemic region for scrub typhus in Shandong Province, but the seriousness of this problem has been neglected in public health circles.
Methodology/Principal Findings
A disability-adjusted life years (DALYs) approach was adopted to measure the burden of scrub typhus in Laiwu, China during the period 2006 to 2012. A multiple seasonal autoregressive integrated moving average model (SARIMA) was used to identify the most suitable forecasting model for scrub typhus in Laiwu. Results showed that the disease burden of scrub typhus is increasing yearly in Laiwu, and which is higher in females than males. For both females and males, DALY rates were highest for the 60–69 age group. Of all the SARIMA models tested, the SARIMA(2,1,0)(0,1,0)12 model was the best fit for scrub typhus cases in Laiwu. Human infections occurred mainly in autumn with peaks in October.
Conclusions/Significance
Females, especially those of 60 to 69 years of age, were at highest risk of developing scrub typhus in Laiwu, China. The SARIMA (2,1,0)(0,1,0)12 model was the best fit forecasting model for scrub typhus in Laiwu, China. These data are useful for developing public health education and intervention programs to reduce disease.
Author Summary
Scrub typhus, also known as tsutsugamushi disease, is a zoonosis transmitted by chigger bites (larval trombiculid mites) and the pathogen Orientia tsutsugamushi (O. tsutsugamushi), a Gram-negative obligate intracellular bacterium. It is distributed widely in the Pacific regions of Asia, and the islands of the western Pacific and Indian Oceans. People with outdoor activities that involve contact with grasses or shrubs are at highest risk. Scrub typhus has existed in Southern China for thousands of years, but it has been noted to spread from the South to the North of China in recent decades. Though this research we studied the disease burden of scrub typhus with disability-adjusted life years (DALYs), and developed a forecasting time series model for human clinical disease in Laiwu, China. Results demonstrated that the disease burden of scrub typhus was increasing year by year in Laiwu, and it was higher in females than males. Moreover, DALY rates in females and males were highest for persons in the 60–69 years age group. Of all the seasonal autoregressive integrated moving average (SARIMA) models tested, the SARIMA(2,1,0)(0,1,0)12 model was the best fit for scrub typhus cases in Laiwu. The disease occurred mainly in autumn, with a peak in October.
doi:10.1371/journal.pntd.0003420
PMCID: PMC4288724  PMID: 25569248
2.  Association between male infertility and either the +331G/A or the progins polymorphism of the progesterone receptor gene in a Chinese population 
Background:
Progesterone has been suggested to contribute to the regulation of spermatogenesis and to facilitate the production of viable sperm. Investigations have showed that polymorphism of progesterone receptor (PGR) is associated with some diseases.
Objective:
To analyze the potential relationship between male infertility and the +331G/A and progins polymorphisms of PGR gene.
Materials and Methods:
The cross-sectional study was carried out at the Department of Male Reproduction, Reproductive Medical Center, the Second Hospital of Jilin University. The restriction fragment length polymorphism (RFLP) technique was used to detect gene point mutations. Of the 145 semen samples analyzed, 35 were asthenozoospermic, 50 were oligoasthenozoospermic, 21 were azoospermic, 11 were teratozoospermic and 28 were from fertile male subjects.
Results:
Statistical analyses revealed that the genotypes of the +331G/A polymorphisms were in Hardy-Weinberg equilibrium in both the fertile (2=0, p=0.534) and oligospermic groups (2=0.021, p=0.537). Similarly, the genotypes of the progins polymorphisms were also in Hardy–Weinberg equilibrium in both the fertile (2=0, p=1) and oligospermic groups (2=0.005, p=1).
Conclusion:
Our results indicated that polymorphisms of the +331G/A and progins of the PGR gene are unrelated to male infertility, at least in a Chinese population.
PMCID: PMC4306983  PMID: 25653674
Progesterone receptor; +331G/A polymorphism; Progins polymorphism; Male infertility
3.  Influential Factors of Insufficient Physical Activity among Adolescents with Asthma in Taiwan 
PLoS ONE  2014;9(12):e116417.
Purpose
Little research has been reported concerning insufficient physical activity in Taiwanese adolescents with asthma. The aims of this paper are to compare the amount of physical activity between asthmatic and non-asthmatic adolescents in Taiwan, as well as to investigate the influential factors associated with insufficient physical activity in asthmatic adolescents.
Methods
Self-reporting structured questionnaires (socio-economic status, scale of family support for physical activity, amount of physical activity) and peak expiratory flow were assessed from 286 adolescents with asthma and 588 non-asthmatic adolescents in a cross-sectional design. Insufficient amount of physical activity was based on less than 300 minutes per week of moderate and vigorous physical activity.
Results
Adolescents with asthma have a greater amount of physical activity and a higher level of family support than those who are non-asthmatic. In Taiwan, adolescents with asthma, girls relative to boys, obesity relative to average weight, and low family support relative to high family support were found to be associated with insufficient physical activity.
Conclusion
Physical activity in adolescents with asthma is insufficient especially in girls, in asthmatics with obesity, and in those with low family support. We suggest that physical activity programs should be applied to Taiwan adolescents with asthma in order to match the criteria of 300 minutes per week of moderate and vigorous physical activity, especially for girls, the obese and those with a low level of family support.
doi:10.1371/journal.pone.0116417
PMCID: PMC4281071  PMID: 25551759
4.  Adult T-Cell Lymphoma/Leukemia Presenting as Isolated Central Nervous System T-Cell Lymphoma 
Case Reports in Hematology  2014;2014:917369.
Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central nervous system (CNS) involved by ATLL is often occurred in advanced disease, such as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is rare. We repot a 50-year-old woman who presented with multiple infiltrative brain lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of brain tumor indicated CNS vasculitis. The patient received one course of high-dose methotrexate and MR imaging of brain revealed remission of infiltrative lesions. Two years later, new brain lesions were detected. Histopathologic examination of specimens via craniotomy revealed T-cell lymphoma. The patient responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation was performed. Six months later, the patient had hepatosplenomegaly, hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in circulation. Results of flow cytometry analysis of peripheral blood indicated ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected. Clinicians should screen HTLV-1 infection when patients are diagnosed with peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy may improve the outcomes of ATLL.
doi:10.1155/2014/917369
PMCID: PMC4284927  PMID: 25587470
5.  Supervised calibration relies on the multisensory percept 
Neuron  2013;80(6):10.1016/j.neuron.2013.09.026.
SUMMARY
Multisensory plasticity enables us to dynamically adapt sensory cues to one another and to the environment. Without external feedback, “unsupervised” multisensory calibration reduces cue conflict in a manner largely independent of cue-reliability. But environmental feedback regarding cue-accuracy (“supervised”) also affects calibration. Here we measured the combined influence of cue-accuracy and cue-reliability on supervised multisensory calibration, using discrepant visual and vestibular motion stimuli. When the less-reliable cue was inaccurate, it alone got calibrated. However, when the more-reliable cue was inaccurate, cues were yoked and calibrated together in the same direction. Strikingly, the less-reliable cue shifted away from external feedback, becoming less accurate. A computational model in which supervised and unsupervised calibration work in parallel, where the former only relies on the multisensory percept, but the latter can calibrate cues individually, accounts for the observed behavior. In combination, they could ultimately achieve the optimal solution of both external accuracy and internal consistency.
doi:10.1016/j.neuron.2013.09.026
PMCID: PMC3872253  PMID: 24290205
macaque monkey; cue combination; optic flow; vestibular; Bayesian; adaptation; calibration; learning; plasticity; psychophysics
6.  Obesity and Its Relationship with Hypertension among Adults 50 Years and Older in Jinan, China 
PLoS ONE  2014;9(12):e114424.
Background
The relationship between obesity and hypertension varies with geographical area, race and definitions of obesity. Our study aimed to investigate the prevalence of obesity using standard Chinese criteria based on the body mass index (BMI) and the waist circumference (WC) and to examine the association between obesity and hypertension among middle-aged and elderly people in Jinan city.
Methods
This cross-sectional study examined 1,870 subjects from the blocks randomly selected from among the 6 communities of Jinan, China in 2011–2012. The Student's t-test was used to compare numerical data, and the χ2 test was used to compare categorical data. Multivariate logistic regression analyses were performed to assess the effects of general and central obesity on hypertension after adjusting for age or for education level, smoking, alcohol consumption, and continuous age.
Results
The prevalence of general obesity among people age 50 years and older was 21.1% (17.0% for males and 23.1% for females), and the prevalence of central obesity was 77.8% for men and 78.7% for women. For men, compared with a normal BMI, the ORs and 95% CIs for overweight and general obesity were 1.853 (1.252, 2.744) and 3.422 (1.894, 6.182), respectively, after adjusting for age, smoking, alcohol consumption and educational level. Compared with a normal WC, the ORs and 95% CIs for central obesity were 2.334 (1.573, 3.465) and 2.318 (1.544, 3.479), respectively, for men. For women, compared with a normal BMI, the ORs and 95% CIs were 1.942 (1.473, 2.599) and 4.011 (2.817, 5.712), respectively, after adjusting for age, smoking, alcohol consumption and educational level. Compared with a normal WC, the ORs and 95% CIs for central obesity were 2.488 (1.865, 3.319) and 2.379 (1.773, 3.192), respectively, for women.
Conclusions
The relationship between hypertension and general obesity was stronger than the relationship between hypertension and either overweight or central obesity in both genders.
doi:10.1371/journal.pone.0114424
PMCID: PMC4269412  PMID: 25517735
7.  The application of vWF/ADAMTS13 in essential hypertension 
Background: Plasma von Willebrand factor (vWF), a key player in hemostasis and thrombosis, is released from endothelial cells during inflammation. Hypertension, a progressing in chronic inflammation and cardiovascular syndrome with various causes, results in functional and structural changes of heart and arterial vessels. However little information is available on LA changes during hypertension. Left atrial (LA) enlargement is associated with significant cardiovascular morbidity and mortality. The aim of this study was to explore the relationship between LA enlargement and thromboembolic risk in essential hypertensive patients with Af without any signs of clinical thrombotic disease or previous stroke. Methods: The relationship between Plasma vWF, ADAMTS13 and left atrial diameter (LAD), left atrial volume (LAV), left atrial volume index (LAVi) were evaluated in essential hypertensive group included 105 patients (55 patients with nonvalvular atrial fibrillation (AF) and 50 patients with normal sinus rhythm (NSR)). Results: The study demonstrated that vWF, vWF/ADAMT13, LAD, LAV and LAVi were increased significantly (P < 0.01) but ADAMTS13: Ag was decreased significantly (P < 0.01) in the hypertensive with AF group compared with NSR group. Conclusion: vWF/ADAMTS13 were positively correlated with LAD, LAV and LAVi (P < 0.01). Increased vWF and vWF/ADAMTS13 is associated with LAD, LAV and LAVi in essential hypertension. The study suggests it played a positive role of vWF and vWF/ADAMTS13 in the progressing major adverse cardiovascular events (MACE) in essential hypertensive patients with LA enlargement.
PMCID: PMC4307530  PMID: 25664083
Echocardiography; essential hypertension; left atrium; vWF-ADAMTS13
8.  Aggregation and morphology control enables multiple cases of high-efficiency polymer solar cells 
Nature Communications  2014;5:5293.
Although the field of polymer solar cell has seen much progress in device performance in the past few years, several limitations are holding back its further development. For instance, current high-efficiency (>9.0%) cells are restricted to material combinations that are based on limited donor polymers and only one specific fullerene acceptor. Here we report the achievement of high-performance (efficiencies up to 10.8%, fill factors up to 77%) thick-film polymer solar cells for multiple polymer:fullerene combinations via the formation of a near-ideal polymer:fullerene morphology that contains highly crystalline yet reasonably small polymer domains. This morphology is controlled by the temperature-dependent aggregation behaviour of the donor polymers and is insensitive to the choice of fullerenes. The uncovered aggregation and design rules yield three high-efficiency (>10%) donor polymers and will allow further synthetic advances and matching of both the polymer and fullerene materials, potentially leading to significantly improved performance and increased design flexibility.
Polymer solar cells promise a cost-effective way to harness solar energy, but cell performance is held back by limited choices of suitable materials. Here, Liu et al. demonstrate record cell efficiencies for multiple material combinations via a new approach of aggregation and morphology control.
doi:10.1038/ncomms6293
PMCID: PMC4242436  PMID: 25382026
9.  Simultaneous Determination of Uric Acid and Xanthine Using a Poly(Methylene Blue) and Electrochemically Reduced Graphene Oxide Composite Film Modified Electrode 
Poly(methylene blue) and electrochemically reduced graphene oxide composite film modified electrode (PMB-ERGO/GCE) was successfully fabricated by electropolymerization and was used for simultaneous determination of uric acid (UA) and xanthine (Xa). Based on the excellent electrocatalytic activity of PMB-ERGO/GCE, the electrochemical behaviors of UA and Xa were studied by cyclic voltammetry (CV) and square wave voltammetry (SWV). Two anodic sensitive peaks at 0.630 V (versus Ag/AgCl) for UA and 1.006 V (versus Ag/AgCl) for Xa were given by CV in pH 3.0 phosphate buffer. The calibration curves for UA and Xa were obtained in the range of 8.00 × 10−8~4.00 × 10−4 M and 1.00 × 10−7~4.00 × 10−4 M, respectively, by SWV. The detection limits for UA and Xa were 3.00 × 10−8 M and 5.00 × 10−8 M, respectively. Finally, the proposed method was applied to simultaneously determine UA and Xa in human urine with good selectivity and high sensitivity.
doi:10.1155/2014/984314
PMCID: PMC4244694  PMID: 25436174
10.  Biomechanical comparison of pedicle screws versus spinous process screws in C2 vertebra 
Indian Journal of Orthopaedics  2014;48(6):550-554.
Background:
Biomechanical studies have shown C2 pedicle screw to be the most robust in insertional torque and pullout strength. However, C2 pedicle screw placement is still technically challenging. Smaller C2 pedicles or medial localization of the vertebral artery may preclude safe C2 pedicle screw placement in some patients. The purpose of this study was to compare the pullout strength of spinous process screws with pedicle screws in the C2.
Materials and Methods:
Eight fresh human cadaveric cervical spine specimens (C2) were harvested and subsequently frozen to −20°C. After being thawed to room temperature, each specimen was debrided of remaining soft tissue and labeled. A customs jig as used to clamp each specimen for screw insertion firmly. Screws were inserted into the vertebral body pairs on each side using one of two methods. The pedicle screws were inserted in usual manner as in previous biomechanical studies. The starting point for spinous process screw insertion was located at the junction of the lamina and the spinous process and the direction of the screw was about 0° caudally in the sagittal plane and about 0° medially in the axial plane. Each vertebrae was held in a customs jig, which was attached to material testing machine (Material Testing System Inc., Changchun, China). A coupling device that fit around the head of the screw was used to pull out each screw at a loading rate of 2 mm/min. The uniaxial load to failure was recorded in Newton'st dependent test (for paired samples) was used to test for significance.
Results:
The mean load to failure was 387 N for the special protection scheme and 465 N for the protection scheme without significant difference (t = −0.862, P = 0.403). In all but three instances (38%), the spinous process pullout values exceeded the values for the pedicle screws. The working distances for the spinous process screws was little shorter than pedicle screws in each C2 specimen.
Conclusion:
Spinous process screws provide comparable pullout strength to pedicle screws of the C2. Spinous process screws may provide an alternative to pedicle screws fixation, especially with unusual anatomy or stripped screws.
doi:10.4103/0019-5413.144212
PMCID: PMC4232822  PMID: 25404765
C2 vertebrae; screw fixation; spinous process screws; pedicle screws; Spine; cervical vertebrae; cadaver; bone screws
11.  Alternative meiotic chromatid segregation in the holocentric plant Luzula elegans 
Nature Communications  2014;5:4979.
Holocentric chromosomes occur in a number of independent eukaryotic lineages. They form holokinetic kinetochores along the entire poleward chromatid surfaces, and owing to this alternative chromosome structure, species with holocentric chromosomes cannot use the two-step loss of cohesion during meiosis typical for monocentric chromosomes. Here we show that the plant Luzula elegans maintains a holocentric chromosome architecture and behaviour throughout meiosis, and in contrast to monopolar sister centromere orientation, the unfused holokinetic sister centromeres behave as two distinct functional units during meiosis I, resulting in sister chromatid separation. Homologous non-sister chromatids remain terminally linked after metaphase I, by satellite DNA-enriched chromatin threads, until metaphase II. They then separate at anaphase II. Thus, an inverted sequence of meiotic sister chromatid segregation occurs. This alternative meiotic process is most likely one possible adaptation to handle a holocentric chromosome architecture and behaviour during meiosis.
Conventionally, meiosis depends on a two-step loss of chromosome cohesion that requires distinction between chromosome arms and sister centromeres. Heckmann et al. show that a plant that lacks a single defined centromere overcomes this problem by inverting the sequence of meiotic segregation events.
doi:10.1038/ncomms5979
PMCID: PMC4214429  PMID: 25296379
12.  Characterization of uncommon portosystemic collateral circulations in patients with hepatic cirrhosis 
Oncology Letters  2014;9(1):347-350.
The purpose of the present study was to characterize uncommon portosystemic collateral circulation in hepatic cirrhosis. Portosystemic uncommon collateral circulation (UCC) was detected, characterized and evaluated by a combination of spiral computed tomography angiography, three-dimensional imaging angiography and electronic gastroscopy in patients diagnosed with hepatic cirrhosis. In total, 118 cases with UCC were detected from a pool of 700 hepatic cirrhosis patients with portal hypertension. The incidence was 16.86% and included cases with splenic-renal, gastro-renal, paravertebral, retroperitoneal, gastric-splenic and cardio-phrenic angle vein shunts. The occurrence rate of UCC formation increased with the Child-Pugh grade. Compared with common collateral circulations, the incidence of severe esophageal or gastric fundus varicose veins, severe portal hypertensive gastropathy and the incidence of a large quantity of ascites was much lower in the patients with UCC (P<0.01), whereas the incidence of hepatic encephalopathy and chronic elevated blood ammonia levels was significantly higher (P<0.01). The incidence of uncommon portosystemic collateral circulation is extremely common in patients with liver cirrhosis and is associated with the Child-Pugh grades of hepatic function. UCC can aid in the relief of the complications derived from portal hypertension, but it may increase the incidence of hepatic encephalopathy and chronic elevated blood ammonia levels.
doi:10.3892/ol.2014.2626
PMCID: PMC4246606  PMID: 25435990
liver cirrhosis; collateral circulation; hepatic encephalopathy; portal hypertension; esophageal varicosity; gastric fundus varicosity
13.  Changing concepts of working memory 
Nature neuroscience  2014;17(3):347-356.
Working memory is widely considered to be limited in capacity, holding a fixed, small number of items, such as Miller's ‘magical number’ seven or Cowan's four. It has recently been proposed that working memory might better be conceptualized as a limited resource that is distributed flexibly among all items to be maintained in memory. According to this view, the quality rather than the quantity of working memory representations determines performance. Here we consider behavioral and emerging neural evidence for this proposal.
doi:10.1038/nn.3655
PMCID: PMC4159388  PMID: 24569831
14.  Factorial Comparison of Working Memory Models 
Psychological review  2014;121(1):124-149.
Three questions have been prominent in the study of visual working memory limitations: (a) What is the nature of mnemonic precision (e.g., quantized or continuous)? (b) How many items are remembered? (c) To what extent do spatial binding errors account for working memory failures? Modeling studies have typically focused on comparing possible answers to a single one of these questions, even though the result of such a comparison might depend on the assumed answers to both others. Here, we consider every possible combination of previously proposed answers to the individual questions. Each model is then a point in a 3-factor model space containing a total of 32 models, of which only 6 have been tested previously. We compare all models on data from 10 delayed-estimation experiments from 6 laboratories (for a total of 164 subjects and 131,452 trials). Consistently across experiments, we find that (a) mnemonic precision is not quantized but continuous and not equal but variable across items and trials; (b) the number of remembered items is likely to be variable across trials, with a mean of 6.4 in the best model (median across subjects); (c) spatial binding errors occur but explain only a small fraction of responses (16.5% at set size 8 in the best model). We find strong evidence against all 6 documented models. Our results demonstrate the value of factorial model comparison in working memory.
doi:10.1037/a0035234
PMCID: PMC4159389  PMID: 24490791
working memory; short-term memory; model comparison; capacity; resource models
15.  Primary hepatic malignant fibrous histiocytoma mimicking hepatocellular carcinoma: A report of two cases 
Oncology Letters  2014;8(5):2150-2154.
Malignant fibrous histiocytoma (MFH) is a tumor that occurs throughout the body as a relatively uncommon entity. The current study presents two cases of primary malignant fibrous histiocytoma of the liver. The first case was of a 67-year-old male who exhibited no symptoms or abnormal physical signs, and in whom the lesion was found by ultrasound examination during a routine physical examination. The second case was of a 35-year-old male who presented with persistent malaise, weight loss and intermittent right upper quadrant pain. The presence of liver cirrhosis due to hepatitis B virus, which was identified 10 years previously, and the clinical appearance caused MFH to appear as hepatocellular carcinoma at the time of the initial diagnosis. Abdominal magnetic resonance imaging scans were the main tools of diagnosis, but the MFH mimicked hepatocellular carcinoma due to the similar morphological characteristics, the rare occurrence of MFH and the underlying diseases of the liver. The first patient underwent a complete resection and recovered well, while the second patient underwent palliative treatment due to the large size of the tumor and the obstructive emboli in the portal vein. The diagnoses of the tumors were confirmed as MFH by histopathology and immunohistochemistry.
doi:10.3892/ol.2014.2483
PMCID: PMC4186583  PMID: 25295102
malignant fibrous histiocytoma; histology; magnetic resonance imaging
16.  A retrospective study: the prevalence and prognostic value of anemia in patients undergoing radiotherapy for esophageal squamous cell carcinoma 
Background
The relationship between anemia and outcomes after radiotherapy has not been systematically addressed. The study aimed to assess the prevalence and prognostic value of anemia in patients receiving primary radiotherapy for esophageal squamous cell carcinoma (ESCC).
Methods
A total of 103 patients with ESCC were retrospectively reviewed. Anemia was defined as a hemoglobin level <12 g/dl for men and <11 g/dl for women. The 3-year and 5-year overall survival (OS) and disease-free survival (DFS) were analyzed between the anemic and non-anemic groups using the Kaplan-Meier method and the Cox proportional hazards model.
Results
No significant differences were observed in patient characteristics between the anemic and non-anemic groups. The prevalence of anemia was 29.1%. The 3-year and the 5-year OS were 43% and 37%, respectively, in the non-anemic group, and 20% and 17%, respectively, in the anemic group. The 3-year and the 5-year DFS were 37% and 26%, respectively, in the non-anemic group, and 13% and 10%, respectively, in the anemic group. Survival analysis using the Kaplan-Meier method showed that there was significant difference between anemia and non-anemia (P < 0.02). In a multivariate analysis, anemia was identified as a highly significant prognostic factor for 3-year OS (hazard ratio 1.916; P = 0.012) and 3-year DFS (hazard ratio 1.973; P = 0.007), independent of T stage and the status of lymph nodes, and 5-year OS (hazard ratio 1.705; P = 0.027) and 5-year DFS (hazard ratio 1.980; P = 0.005), independent of TNM stage and the status of lymph nodes.
Conclusions
Anemia before primary radiotherapy was associated with poor prognosis and an increased risk of relapse, which may serve as a new prognostic factor for ESCC.
doi:10.1186/1477-7819-12-244
PMCID: PMC4126388  PMID: 25085112
Anemia; Survival; Prevalence; Esophageal neoplasms; Squamous cell carcinoma; Radiotherapy
17.  The Use of Mixed Generalized Additive Modeling to Assess the Effect of Temperature on the Usage of Emergency Electrocardiography Examination among the Elderly in Shanghai 
PLoS ONE  2014;9(6):e100284.
Background
Acute coronary artery diseases have been observed to be associated with some meteorological variables. But few of the previous studies considered autocorrelated outcomes. Electrocardiography is a widely used tool in the initial diagnosis of acute cardiovascular events, and emergency electrocardiography counts were shown to be highly correlated with acute myocardial infarction in our pilot study, hence a good index of prediction for acute cardiovascular events morbidity among the elderly. To indirectly assess the impact of temperature on the number of acute cardiovascular events, we studied the association between temperature and emergency electrocardiography counts while considering autocorrelated nature of the response variables.
Methods
We collected daily emergency electrocardiography counts for elderly females and males in Shanghai from 2007 to middle 2012, and studied temperature and other effects on these data using Mixed Generalized Additive Modelling methods. Delayed temperature effect distribution was described as the weighted average of the temperatures within 3 days before the counts was recorded. Autoregressive random effects were used in the model to describe the autocorrelation of the response variables.
Main Results
Temperature effect was observed to be piecewise linearly associated with the logarithm of emergency electrocardiography counts. The optimal weights of the delayed temperature effect distribution were obtained from the model estimation. The weights of lag-1 were the maximums, significantly greater than the weights of lag-2 and lag-3 for both females and males. The model showed good fit with R2 values of 0.860 for females and 0.856 for males.
Conclusion
From the mixed generalized additive model, we infer that during cold and mild days, the number of emergency electrocardiography counts increase as temperature effect decreases, while during hot days, counts increase as temperature effect increases. Similar properties could be inferred for the occurrence of cardiovascular events.
doi:10.1371/journal.pone.0100284
PMCID: PMC4061122  PMID: 24936868
18.  MALDI-TOF-MS serum protein profiling for developing diagnostic models and identifying serum markers for discogenic low back pain 
Background
The identification of the cause of chronic low back pain (CLBP) represents a great challenge to orthopedists due to the controversy over the diagnosis of discogenic low back pain (DLBP) and the existence of a number of cases of CLBP of unknown origin. This study aimed to develop diagnostic models to distinguish DLBP from other forms of CLBP and to identify serum biomarkers for DLBP.
Methods
Serum samples were collected from patients with DLBP, chronic lumbar disc herniation (LDH), or CLBP of unknown origin, and healthy controls (N), and randomly divided into a training set (n = 30) and a blind test set (n = 30). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed for protein profiling of these samples. After the discriminative ability of two most significantly differential peaks from each two groups was assessed using scatter plots, classification models were developed using differential peptide peaks to evaluate their diagnostic accuracy. The identity of peptides corresponding to three representative differential peaks was analyzed.
Results
The fewest statistically significant differential peaks were identified between DLBP and CLBP (3), followed by CLBP vs. N (5), DLBP vs. N (9), LDH vs. CLBP (20), DLBP vs. LDH (23), and LDH vs. N (43). The discriminative ability of two most significantly differential peaks was poor in classifying DLBP vs. CLBP but good in classifying DLBP vs. LDH. The accuracy of models for classification of DLBP vs. CLBP was not very high in the blind test (forecasting ability, 67.24%; sensitivity, 70%), although a higher accuracy was observed for classification of DLBP vs. LDH and LDH vs. N (forecasting abilities, ~90%; sensitivities, >90%). A further investigation of three representative differential peaks led to the identification of two peaks as peptides of complement C3, and one peak as a human fibrinogen peptide.
Conclusions
Our findings benefit not only the diagnosis of CLBP but also the understanding of the differences between different forms of DLBP. The ability to distinguish between different causes of CLBP and the identification of serum biomarkers may be of great value to diagnose different causes of DLBP and predict treatment efficacy.
doi:10.1186/1471-2474-15-193
PMCID: PMC4061098  PMID: 24889399
Chronic low back pain; Dicogenic low back pain; Lumbar disc herniation; MALDI-TOF-MS; Serum profiling; Biomarker
19.  High-Throughput Analysis and Characterization of Astragalus membranaceus Transcriptome Using 454 GS FLX 
PLoS ONE  2014;9(5):e95831.
Astragalus membranaceus (Fisch.) Bge (AR), one of the most important medicinal plants in Asia, was found to exhibit various bioactivities. Due to limited genomic and transcriptomic data, the biosynthetic pathway of the major bioactive compound in AR, is currently unclear. In this study, 454 GS FLX technology was employed to produce a substantial expressed sequence tag (EST) dataset from the AR. In all, 742721 high-quality reads from the AR were produced using Roche GS FLX Titanium. A total of 9893 unique sequences were obtained and annotated by a similarity search against the public databases, and involved in the secondary metabolic pathway, which would facilitate deciphering the molecular mechanism of secondary metabolism in AR. The assembled sequences were annotated with gene names and Gene Ontology (GO) terms. GO revealed the unique sequences that could be assigned to 34 vocabularies. In the KEGG mapping, unique sequences were established as associated with 46 biochemical pathways. These results provided the largest EST collections in AR and will contribute to biosynthetic and biochemical studies that lead to drug improvement. With respect to the genes related to metabolism and biosynthesis pathway were also found. Our work demonstrated the utility of 454 GS FLX as a method for the rapid and cost-effective identification of AR transcriptome, and this EST dataset will be a powerful resource for further studies such as taxonomy, molecular breeding, and secondary metabolism in AR.
doi:10.1371/journal.pone.0095831
PMCID: PMC4020759  PMID: 24828103
20.  Deep Sea Water Prevents Balloon Angioplasty-Induced Hyperplasia through MMP-2: An In Vitro and In Vivo Study 
PLoS ONE  2014;9(5):e96927.
Major facts about the development of restenosis include vascular smooth muscle cells (VSMCs) proliferation and migration. A previous study showed that in vitro treatment with magnesium chloride has the potential to affect the proliferation and migration of VSMCs. Magnesium is the major element in deep sea water (DSW) and is a biologically active mineral. It is unclear whether DSW intake can prevent abnormal proliferation and migration of VSMCs as well as balloon angioplasty-induced neointimal hyperplasia. Thus, we attempted to evaluate the anti-restenotic effects of DSW and its possible molecular mechanisms. Several concentrations of DSW, based on the dietary recommendations (RDA) for magnesium, were applied to a model of balloon angioplasty in SD rats. The results showed that DSW intake markedly increased magnesium content within the vascular wall and reduced the development of neointimal hyperplasia. The immunohistochemical analysis also showed that the expression of proteins associated with cell proliferation and migration were decreased in the balloon angioplasty groups with DSW supplement. Furthermore, in vitro treatment with DSW has a dose-dependent inhibitory effect on serum-stimulated proliferation and migration of VSMCs, whose effects might be mediated by modulation of mitogen-activated protein kinase (MAPK) signaling and of the activity of matrix metalloproteinase-2 (MMP-2). Our study suggested that DSW intake can help prevent neointimal hyperplasia (or restenosis), whose effects may be partially regulated by magnesium and other minerals.
doi:10.1371/journal.pone.0096927
PMCID: PMC4019650  PMID: 24824358
21.  Introducing rapid oral–fluid HIV testing among high risk populations in Shandong, China: feasibility and challenges 
BMC Public Health  2014;14:422.
Background
This study was conducted to ascertain the feasibility of using rapid oral fluid testing as an alternative HIV testing method in China.
Method
This is a mixed-method study among men who have sex with men (MSM), female sex workers (FSW) and VCT clients, conducted in 4 cities in Shandong Province. A pre-tested questionnaire was administered to 1137 participants through face-to-face interview to assess demographic characteristics, HIV testing histories and willingness to accept rapid oral fluid testing. VCT clients were provided with the saliva test kits for a screening test and errors in operation were recorded. Testing results were compared between oral and blood testing. Short feedback questionnaire was administered to 200 FSW who had undergone oral testing.
Results
The rate of willingness to take oral-fluid HIV testing among MSM, FSW and VCT clients was 72.8%, 72.1% and 67.4% respectively. Common errors recorded during test kit operation by the 229 VCT clients included: unpreparedness, wrong swab sampling, wrong dilution, wrong testing and inability to read test results. Advantages of oral testing listed by participants included: less intrusive, painlessness, easy self- testing and privacy. Disadvantages included perceived unreliable results (55.5%) and not nationally recognised (9%). Comparison of saliva and the blood testing results recorded a consistency rate of 0.970 (χ2 = 153.348, P < 0.001), implying an excellent consistency.
Conclusion
Introduction of oral rapid fluid testing as an alternative HIV testing method in China is highly feasible but with some challenges including low recognition and operation errors.
doi:10.1186/1471-2458-14-422
PMCID: PMC4045859  PMID: 24884431
HIV/AIDS; Rapid oral fluid test; Saliva testing; Feasibility and acceptance; China
22.  Inhibition of Activator Protein 1 Activity and Neoplastic Transformation by Aspirin* 
The Journal of biological chemistry  1997;272(15):9962-9970.
Aspirin, along with its analgesic-antipyretic uses, is now also being considered for prevention of cardiovascular disease, cancer, and treatment of human immunodeficiency virus infection. Although many of aspirin's pharmacological actions are related to its ability to inhibit prostaglandin biosynthesis, some of its beneficial therapeutic effects are not completely understood. Transcription factor activator protein 1 (AP-1) is critical for the induction of neoplastic transformation and induction of multiple genes involved in inflammation and infection. We have used the JB6 mouse epidermal cell lines, a system that has been used extensively as an in vitro model for the study of tumor promotion and anti-tumor promotion, to study the anti-carcinogenesis effect of aspirin at the molecular level. Aspirin and aspirin-like salicylates inhibited the activation of AP-1 in the same dose range as seen for the inhibition of tumor promoter-induced transformation. The inhibition of AP-1 and tumor promoter-induced transformation in JB6 cells occurs through a prostaglandin independent- and an Erk1- or Erk2-independent pathway. The mechanism of AP-1 and transformation inhibition in this cell culture model may involve the elevation of H+ concentration. The inhibition effects on the activation of AP-1 activity by aspirin and aspirin-like salicylates may further explain the anti-carcinogenesis mechanism of action of these drugs.
PMCID: PMC4003901  PMID: 9092536
23.  Clinicopathology significance of podoplanin immunoreactivity in esophageal squamous cell carcinoma 
Backgroud and aim: Podoplanin (D2-40) is a specific marker for lymphatic endothelium. The vast majority of previous studies on podoplanin immunostaining in esophageal squamous cell carcinoma (ESCC) focused on identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) and had contradictory results. Recent studies show podoplanin expression on cancer cells or tumor stroma in several cancers, which have specific significance; but the status in ESCC remains unclear. Therefore, the aim of this study was to further study and summarize the clinicopathological significance of podoplanin immunoreactivity in ESCC. Materials and methods: We examined podoplanin expression in tissue specimens from 107 patients with ESCC by immunohistochemistry. Podoplanin positive lymphatic vessels in intratumoral and peritumoral tissues and podoplanin positive expression in cancer cells and tumor stroma were analyzed, and correlated with clinicopathologic parameters and three-year overall and free-disease survival. Results: 34 (31.8%) and 28 (26.2%) of 107 specimens had podoplanin positive expression in cancer cells and tumor stroma, respectively. Logistic regression analysis showed high intratumoral lymphatic vessel density (I-LVD) and podoplanin positivity in cancer cells were increased risks of lymph node metastasis (LNM) (OR = 2.45, P = 0.03; OR = 0.35, P = 0.01, respectively). Survival analysis showed that I-LVD was a significant factor related to poor three-year overall and free-disease survival (P = 0.04, P = 0.03, respectively). Conclusions: Previous data and our results show that podoplanin seems to be a useful marker to predict LNM, recurrence, and worse prognosis in ESCC; in particular, LVI, high I-LVD, and podoplanin positivity in cancer cells are associated with LNM, recurrence and overall survival.
PMCID: PMC4069902  PMID: 24966946
Podoplanin; esophagus; immunohistochemistry; squamous cell carcinoma
24.  HIV Prevention Services and Testing Utilization Behaviors among Men Who Have Sex with Men at Elevated Risk for HIV in Chongqing, China 
BioMed Research International  2014;2014:174870.
Objective. To investigate barriers and correlates of the use of HIV prevention services and HIV testing behaviors among men who have sex with men in Chongqing. Methods. Three consecutive cross-sectional surveys provided demographic, sexual behavior, HIV/syphilis infection, HIV prevention service, and testing behavior data. Results. Of 1239 participants, 15.4% were infected with HIV, incidence was 12.3 per 100 persons/year (95% CI: 9.2–15.3), 38% of the participants reported ever having unprotected insertive anal sex, 40% ever received free condom/lubricants in the past year, and 27.7% ever obtained free sexually transmitted infection examination/treatment in the past year. Multivariable logistic regression revealed that lower levels of HIV/AIDS related stigmatizing/discriminatory attitudes, full-time jobs, and sex debut with men at a younger age were independently associated with use of free condom/lubricants. Large social networks, higher incomes, and sexual debut with men at a younger age were associated with use of any HIV prevention and HIV testing services. Lower levels of stigmatizing/discriminatory attitudes were also associated with HIV testing. Fearing needles and being unaware of the venues for testing were top barriers for testing service utilization. Conclusion. It is imperative to address HIV/AIDS related stigmatizing/discriminatory attitudes and other barriers while delivering intervention and testing services.
doi:10.1155/2014/174870
PMCID: PMC3982458  PMID: 24783195
25.  Serum soluble ST2 is associated with ER-positive breast cancer 
BMC Cancer  2014;14:198.
Background
ST2, a member of the interleukin (IL)-1receptor family, regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions. However, the role of ST2 signaling in tumor growth and metastasis of breast cancers has not been investigated. This study investigated the possible role of soluble ST2 (sST2) in breast cancer.
Methods
The serum levels of IL-33, sST2, and vascular endothelial growth factor (VEGF) in 150 breast cancer patients and 90 healthy women were measured by enzyme-linked immunosorbent assay. Estrogen receptor(ER), progesterone receptor, human epithelial receptor (HER)-2, and cell cycle regulated protein Ki-67 were measured. Clinical stage, tumor size, lymph node metastasis, and histological type were also recorded.
Results
The serum levels of sST2, IL-33, and VEGF were significantly higher in breast cancer patients than in the control group (P < 0.05, each). Serum sST2 levels in ER-positive breast cancer patients were significantly associated with age, histological type, clinical stage, tumor size, and Ki-67 status (P < 0.05, each). Moreover, the serum levels of IL-33 and sST2 in breast cancers significantly correlated with VEGF levels (IL-33: r = 0.375, P < 0.0001; sST2: r = 0.164, P = 0.045). Serum levels of sST2, IL-33, and VEGF decreased after modified radical mastectomy in ER-positive breast cancers. Serum levels of IL-33, sST2, and VEGF and clinicopathological factors were not significantly correlated with disease-free survival and overall survival of ER-positive breast cancer women during follow-up.
Conclusion
Serum sST2 levels in ER-positive breast cancer patients are significantly associated with factors that indicate poor prognosis.
doi:10.1186/1471-2407-14-198
PMCID: PMC3995159  PMID: 24636276
Soluble ST2, sST2; Interleukin-33, IL-33; Vascular endothelial growth factor, VEGF; Breast cancer

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