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1.  Adenoviruses Associated with Acute Diarrhea in Children in Beijing, China 
PLoS ONE  2014;9(2):e88791.
Adenoviruses have been recognized as important causal pathogens of community-acquired diarrhea (CAD) among children, but their role in hospital-acquired diarrhea (HAD) is not well-understood. Hospitalized children with acute diarrhea and children who visited the outpatient department due to diarrhea were investigated from 2011 to 2012. Adenovirus was detected in stool specimens by PCR and further characterized by sequencing and phylogenetic analysis. SPSS software (version 19.0) was used for statistical analyses. A total of 2233 diarrheal children were enrolled in this study; this sample was comprised of 1371 hospitalized children, including 885 with CAD (IP-CAD) and 486 with HAD, and 862 outpatients with CAD (OP-CAD). Among these 2,233 patients, adenovirus was detected in 219 cases (9.8%). The positive rates for adenovirus were significantly different between the IP-CAD (9.3%), HAD (13.8%) and OP-CAD (8.1%) cases (X2 = 11.76, p = 0.003). The positive rate of adenovirus was lower in infants under six months of age compared to the positive rates in the other age groups. Of the 219 of adenovirus positive patients, 91 (41.6%) were identified as having serotype 41. Although enteric adenovirus (group F) was the most frequently detected adenovirus among children with either CAD or HAD, the role of non-enteric adenoviruses, especially the adenovirus 31 type (19.7%), cannot be ignored in diarrheal children.
doi:10.1371/journal.pone.0088791
PMCID: PMC3923065  PMID: 24533149
2.  Analysis of the severity and prognosis assessment of aged patients with community-acquired pneumonia: a retrospective study 
Journal of Thoracic Disease  2013;5(5):626-633.
Background
Community-acquired pneumonia (CAP) is a prevalent and potentially life-threatening infection, and has poor prognosis in aged patients. The objective of this study was to compare the potential of admission N-terminal pro B-type natriuretic peptide (proBNP) levels and scoring models [CURB-65, Pneumonia Severity Index (PSI), and Acute Physiology and Chronic Health Evaluation (APACHE) II scores] to predict outcomes for aged patients with CAP admitted to Intensive Care Unit (ICU), and to explore the prognostic factors.
Methods
Clinical data of the patients were collected retrospectively, whose CURB-65, PSI, APACHE II scores were calculated and in whom measurements of proBNP was performed. The outcomes of interest were severity evaluation, prediction of need for mechanical ventilation and 28-day mortality. Receiver operating characteristic (ROC) curve was conducted to predict the assessment ability of proBNP and scoring models on different outcomes, and the logistic regression analysis was performed to screen factors affecting prognosis.
Results
240 patients were enrolled, with the mean age of 75±8 years old. Admission levels of NT-proBNP, scoring models were significantly higher in SCAP patients, MV group, and non-survivors compared to non-SCAP patients, no-MV group, and 28-day survivors, respectively (P<0.001). PSI had the highest area under the curve (AUC) and specificity for the three outcomes considered (AUC: 0.868 and specificity: 0.906 for 28-day mortality, AUC: 0.864 and specificity: 0.831 for requirement of MV, and AUC: 0.888 and specificity: 0.894 for severity evaluation). NT-proBNP had the highest sensitivity of 0.987 and 0.903 on prediction of mortality and need for MV. And APACHE II scoring model with the highest sensitivity of 0.890 was used to evaluate severity. Logistic regression analysis showed that the odd ratio (OR) of systolic blood pressure, PSI, and APACHE II scores were 0.886, 1.019, and 1.249.
Conclusions
PSI scores was the best indicator in predicting different clinical outcomes of aged patients with CAP among the proBNP and three scoring systems. Systolic blood pressure might be as a protective factor for prognosis while PSI and APACHE II scores as risk factors for prognosis of aged patients with CAP.
doi:10.3978/j.issn.2072-1439.2013.09.10
PMCID: PMC3815733  PMID: 24255776
Aged; community-acquired pneumonia (CAP); severity; prognosis
3.  Genetic Variation in Attachment Glycoprotein Genes of Human Respiratory Syncytial Virus Subgroups A and B in Children in Recent Five Consecutive Years 
PLoS ONE  2013;8(9):e75020.
Human respiratory syncytial virus (HRSV) outranks other viral agents as the cause of respiratory tract diseases in children worldwide. Molecular epidemiological study of the virus provides useful information for the development of globally effective vaccine. We investigated the circulating pattern and genetic variation in the attachment glycoprotein genes of HRSV in Beijing during 5 consecutive seasons from 2007 to 2012. Out of 19,942 tested specimens, 3,160 (15.8%) were HRSV antigen-positive. The incidence of HRSV infection in males was significantly higher than in females. Of the total 723 (23.1%) randomly selected HRSV antigen-positive samples, 462 (63.9%) and 239 (33.1%) samples were identified as subgroup A and B, respectively. Subgroups A and B co-circulated in the 5 consecutive HRSV seasons, which showed a shifting mixed pattern of subgroup dominance. Complete G gene sequences were obtained from 190 HRSV-A and 72 HRSV-B by PCR for phylogenetic analysis. Although 4 new genotypes, NA3 and NA4 for HRSV-A and BA-C and CB1 for HRSV-B, were identified here, they were not predominant; NA1 and BA9 were the prevailing HRSV-A and -B genotypes, respectively. We provide the first report of a 9 consecutive nucleotide insertion in 3 CB1 genotype strains. One Beijing strain of ON1 genotype with a 72 nucleotide insertion was found among samples collected in February 2012. The reversion of codon states in glycosylation sites to previous ones were found from HRSV strains in this study, suggesting an immune-escape strategy of this important virus.
doi:10.1371/journal.pone.0075020
PMCID: PMC3775769  PMID: 24069376
4.  Control of Respiratory Motion by Hypnosis Intervention during Radiotherapy of Lung Cancer I 
BioMed Research International  2013;2013:574934.
The uncertain position of lung tumor during radiotherapy compromises the treatment effect. To effectively control respiratory motion during radiotherapy of lung cancer without any side effects, a novel control scheme, hypnosis, has been introduced in lung cancer treatment. In order to verify the suggested method, six volunteers were selected with a wide range of distribution of age, weight, and chest circumference. A set of experiments have been conducted for each volunteer, under the guidance of the professional hypnotist. All the experiments were repeated in the same environmental condition. The amplitude of respiration has been recorded under the normal state and hypnosis, respectively. Experimental results show that the respiration motion of volunteers in hypnosis has smaller and more stable amplitudes than in normal state. That implies that the hypnosis intervention can be an alternative way for respiratory control, which can effectively reduce the respiratory amplitude and increase the stability of respiratory cycle. The proposed method will find useful application in image-guided radiotherapy.
doi:10.1155/2013/574934
PMCID: PMC3777187  PMID: 24093100
5.  Improved Survival and Reduced Phenotypic Severity Following AAV9/MECP2 Gene Transfer to Neonatal and Juvenile Male Mecp2 Knockout Mice 
Typical Rett syndrome (RTT) is a pediatric disorder caused by loss-of-function mutations in the MECP2 gene. The demonstrated reversibility of RTT-like phenotypes in mice suggests that MECP2 gene replacement is a potential therapeutic option in patients. We report improvements in survival and phenotypic severity in Mecp2-null male mice after neonatal intracranial delivery of a single-stranded (ss) AAV9/CBA-MECP2 vector. Median survival was 16.6 weeks for MECP2-treated versus 9.3 weeks for GFP-treated mice. ssAAV9/CBA-MECP2-treated mice also showed significant improvement in the phenotype severity score, in locomotor function and in exploratory activity, as well as a normalization of neuronal nuclear volume in transduced cells. Wild-type mice receiving neonatal injections of the same ssAAV9/CBA-MECP2 vector did not show any significant deficits, suggesting a tolerance for modest MeCP2 overexpression. To test a MECP2 gene replacement approach in a manner more relevant for human translation, a self-complementary AAV vector designed to drive MeCP2 expression from a fragment of the Mecp2 promoter was injected intravenously into juvenile (4-5 week-old) Mecp2-null mice. While the brain transduction efficiency in juvenile mice was low (~2-4% of neurons), modest improvements in survival were still observed. These results support the concept of MECP2 gene therapy for RTT.
doi:10.1038/mt.2012.200
PMCID: PMC3536818  PMID: 23011033
AAV; Gene Therapy; MeCP2; Rett Syndrome
6.  Effects of Vitamin B6 Therapy for Sepsis Patients with Linezolid-Associated Cytopenias: A Retrospective Study☆ 
Background
The common adverse effects of linezolid for treating septic patients with gram-positive cocci is anemia and thrombocytopenia, which limit its clinical application.
Objectives
We determined the effects of vitamin B6 adjunctive therapy on linezolid-associated cytopenias, and retrospectively studied 75 septic patients who received at least 7 days of linezolid treatment.
Methods
Patients were divided into a linezolid treatment group (LTG; n = 41) that received linezolid only and a combination treatment group (CTG; n = 34) that received both linezolid and vitamin B6. Each group was further subdivided into those with sepsis and those with severe sepsis. Each patient had red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), and platelet (PLT) measurements at baseline (day 0) and every other day for 2 weeks during treatment; these parameters were compared between the groups and assessed for time-dependent trends.
Results
For patients in the LTG, RBC, Hb, and Hct values showed statistically significant reductions over time, and these values were lower compared with the values in the CTG. The CTG also showed downward trends, except on the first day of treatment. The PLT count also decreased in both groups. Patients with severe sepsis had lower PLT counts in both treatment groups compared with the septic patients.
Conclusions
Septic patients who received a combination treatment of linezolid and vitamin B6 might show positive effects for linezolid-associated reductions in some hematologic parameters (RBC, Hb, and Hct). This combined treatment might also slow PLT reduction, which was more evident in patients with severe sepsis. ClinicalTrials.gov identifier: NCT01295801.
doi:10.1016/j.curtheres.2012.12.002
PMCID: PMC3862191  PMID: 24385027
linezolid; linezolid-associated cytopenias; sepsis; vitamin B6
7.  Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice 
Virology Journal  2013;10:162.
Aim
To evaluate the efficacy and safety of Entecavir (ETV) plus adefovir (ADV) for chronic hepatitis B (CHB) patients after multiple nucleos(t)ide analogue (NAs) failure treatment.
Methods
Hepatitis B e antigen (HBeAg)-positive patients who had a suboptimal response or developed resistance to two or more previous NAs treatments were included, and all subjects were treated with ETV in combination with ADV for ≥ 24 months. Complete virologic response (CVR) was defined as an undetectability of serum hepatitis B virus (HBV) DNA level during treatment. Safety assessment was based on the increasing of serum creatinine and creatine kinase levels.
Results
A total of 45 eligible patients were included. Twenty-five patients had been treated with lamivudine (LAM) or telbivudine (LdT) and developed genotypic resistance. Resistance to ADV was present in 18 patients and 4 patients had a suboptimal response to ETV. Two patients had a resistance to both LAM and ADV. The cumulative probabilities of CVR at 12 and 24 months of ETV + ADV treatment were 88.9% (40/45) and 97.8% (44/45), respectively. Although one patient failed to achieve CVR, its serum HBV DNA level decreased by 3.3 log copies/mL after 24 months of combination therapy. The cumulative probability of HBeAg seroconversion was 15.6% (7/45) and 26.7% (12/45) at 12 and 24 months of treatment, respectively. History of prior exposure to specific NAs did not make a difference to ETV + ADV treatment outcome. There were no significant adverse events related to ETV + ADV therapy observed in the study subjects.
Conclusion
ETV + ADV can be used as an effective and safe rescue therapy in patients after multiple NA therapy failures, especially in the areas where tenofovir is not yet available.
doi:10.1186/1743-422X-10-162
PMCID: PMC3680075  PMID: 23706010
Chronic hepatitis B; Multiple failures; Resistance; Combination therapy; Entecavir; Adefovir
8.  Nanoporous CREG-Eluting Stent Attenuates In-Stent Neointimal Formation in Porcine Coronary Arteries 
PLoS ONE  2013;8(4):e60735.
Background
The goal of this study was to evaluate the efficacy of a nanoporous CREG-eluting stent (CREGES) in inhibiting neointimal formation in a porcine coronary model.
Methods
In vitro proliferation assays were performed using isolated human endothelial and smooth muscle cells to investigate the cell-specific pharmacokinetic effects of CREG and sirolimus. We implanted CREGES, control sirolimus-eluting stents (SES) or bare metal stents (BMS) into pig coronary arteries. Histology and immunohistochemistry were performed to assess the efficacy of CREGES in inhibiting neointimal formation.
Results
CREG and sirolimus inhibited in vitro vascular smooth muscle cell proliferation to a similar degree. Interestingly, human endothelial cell proliferation was only significantly inhibited by sirolimus and was increased by CREG. CREGES attenuated neointimal formation after 4 weeks in porcine coronary model compared with BMS. No differences were found in the injury and inflammation scores among the groups. Scanning electron microscopy and CD31 staining by immunohistochemistry demonstrated an accelerated reendothelialization in the CREGES group compared with the SES or BMS control groups.
Conclusions
The current study suggests that CREGES reduces neointimal formation, promotes reendothelialization in porcine coronary stent model.
doi:10.1371/journal.pone.0060735
PMCID: PMC3616099  PMID: 23573278
9.  Expression of WNT-5a and ROR2 correlates with disease severity in osteosarcoma 
Molecular Medicine Reports  2012;5(4):1033-1036.
Osteosarcoma, a common malignancy primarily affecting children, generally has a poor prognosis. Novel diagnostic, prognostic and therapeutic markers are required to ameliorate the negative outcomes of this disease. We investigated two potential markers, WNT-5a and ROR2, which are hypothesized to dysregulate WNT signaling pathways to promote tumorigenesis in other types of cancer. We investigated WNT-5a and ROR2 expression using immunohistochemistry in 42 osteosarcoma and 12 osteochondroma specimens, and compared the expression of these proteins with one another as well as with clinicopathological parameters. WNT-5a was detected in 34/42 (81.0%) cases and ROR2 was detected in 31/42 (73.8%) cases, significantly higher than in osteochondroma (16.7 and 25.0%, respectively; both P<0.05). Expression of these proteins was positively correlated (r=0.552, P<0.05). Furthermore, expression of WNT-5a and ROR2 was both correlated with Enneking surgical stage and tumor metastasis (P<0.05), but not with patient gender, age or pathological type. Thus, WNT-5a and ROR2 were more highly expressed in more severe disease states, and therefore may play a coordinated role in the occurrence and progression of osteosarcoma.
doi:10.3892/mmr.2012.772
PMCID: PMC3493076  PMID: 22293903
osteosarcoma; Wnt-5a; Ror2; immunohistochemistry; clinicopathological parameter
11.  Identification of Novel Biomarkers for Sepsis Prognosis via Urinary Proteomic Analysis Using iTRAQ Labeling and 2D-LC-MS/MS 
PLoS ONE  2013;8(1):e54237.
Objectives
Sepsis is the major cause of death for critically ill patients. Recent progress in proteomics permits a thorough characterization of the mechanisms associated with critical illness. The purpose of this study was to screen potential biomarkers for early prognostic assessment of patients with sepsis.
Methods
For the discovery stage, 30 sepsis patients with different prognoses were selected. Urinary proteins were identified using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS. Mass spec instrument analysis were performed with Mascot software and the International Protein Index (IPI); bioinformatic analyses were used by the algorithm of set and the Gene Ontology (GO) Database. For the verification stage, the study involved another 54 sepsis-hospitalized patients, with equal numbers of patients in survivor and non-survivor groups based on 28-day survival. Differentially expressed proteins were verified by Western Blot.
Results
A total of 232 unique proteins were identified. Proteins that were differentially expressed were further analyzed based on the pathophysiology of sepsis and biomathematics. For sepsis prognosis, five proteins were significantly up-regulated: selenium binding protein-1, heparan sulfate proteoglycan-2, alpha-1-B glycoprotein, haptoglobin, and lipocalin; two proteins were significantly down-regulated: lysosome-associated membrane proteins-1 and dipeptidyl peptidase-4. Based on gene ontology clustering, these proteins were associated with the biological processes of lipid homeostasis, cartilage development, iron ion transport, and certain metabolic processes. Urinary LAMP-1 was down-regulated, consistent with the Western Blot validation.
Conclusion
This study provides the proteomic analysis of urine to identify prognostic biomarkers of sepsis. The seven identified proteins provide insight into the mechanism of sepsis. Low urinary LAMP-1 levels may be useful for early prognostic assessment of sepsis.
Trial Registration
ClinicalTrial.gov NCT01493492
doi:10.1371/journal.pone.0054237
PMCID: PMC3553154  PMID: 23372690
12.  Voices from the Shadows: Living with Lymphedema 
Cancer nursing  2012;35(1):E18-E26.
Background
Breast cancer survivors with lymphedema face a lifetime of stressful physical and emotional symptoms and challenging self-care demands. An in-depth understanding of the perceptions and feelings surrounding life with lymphedema is critical to developing effective supportive care approaches.
Objective
To explore perceptions and feelings related to lymphedema in breast cancer survivors.
Method
The expressive writings of 39 individuals were evaluated for this descriptive qualitative study. Data were analyzed using conventional content analysis.
Results
Qualitative analyses produced four major themes: (1) marginalization and minimization; (2) multiplying losses; (3) yearning to return to normal; (4) uplifting resources. Sub-themes for each major theme were also identified.
Conclusion
The lymphedema experiences of breast cancer survivors reveal perceptions of marginalization from healthcare providers who are not well informed about lymphedema management and minimize its impact. Multiple distressing losses confront these patients on a daily basis, including body image disturbances, loss of functionality and control over time, permanent uncertainty, and adverse effects on relationships. The daily challenges of lymphedema often result in cumulative frustration and resentment that contribute to failure to perform self-care. Normalcy has been lost, never to return. These women find solace, encouragement and hope to meet the challenges of lymphedema through support from others and their spiritual beliefs.
Implication for Practice
Healthcare providers need greater awareness of the physical and psychosocial effects of lymphedema in breast cancer survivors. Nurses have unique opportunities to serve as advocates for reducing perceived marginalization and promoting effective self-care and other activities that promote psychological well-being and reduce physical deterioration.
doi:10.1097/NCC.0b013e31821404c0
PMCID: PMC3172392  PMID: 21558848
Lymphedema; Breast Cancer; Marginalization; Psychosocial Stress; Cancer Treatment Late-effects; Qualitative Research; Women’s Health
13.  Differential Regulation of MeCP2 Phosphorylation in the CNS by Dopamine and Serotonin 
Neuropsychopharmacology  2011;37(2):321-337.
Systemic administration of amphetamine (AMPH) induces phosphorylation of MeCP2 at Ser421 (pMeCP2) in select populations of neurons in the mesolimbocortical brain regions. Because AMPH simultaneously activates multiple monoamine neurotransmitter systems, here we examined the ability of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) to induce pMeCP2. Selective blockade of the DA transporter (DAT) or the 5-HT transporter (SERT), but not the NE transporter (NET), was sufficient to induce pMeCP2 in the CNS. DAT blockade induced pMeCP2 in the prelimbic cortex (PLC) and nucleus accumbens (NAc), whereas SERT blockade induced pMeCP2 only in the NAc. Administration of selective DA and 5-HT receptor agonists was also sufficient to induce pMeCP2; however, the specific combination of DA and 5-HT receptors activated determined the regional- and cell-type specificity of pMeCP2 induction. The D1-class DA receptor agonist SKF81297 induced pMeCP2 widely; however, coadministration of the D2-class agonist quinpirole restricted the induction of pMeCP2 to GABAergic interneurons of the NAc. Intra-striatal injection of the adenylate cyclase activator forskolin was sufficient to induce pMeCP2 in medium-spiny neurons, suggesting that the combinatorial regulation of cAMP by different classes of DA and 5-HT receptors may contribute to the cell-type specificity of pMeCP2 induction. Consistent with the regulation of pMeCP2 by multiple monoamine neurotransmitters, genetic disruption of any single monoamine transporter in DAT-, SERT-, and NET-knockout mice failed to eliminate AMPH-induced pMeCP2 in the NAc. Together, these studies indicate that combinatorial signaling through DA and 5-HT receptors can regulate the brain region- and cell-type specific pMeCP2 in the CNS.
doi:10.1038/npp.2011.190
PMCID: PMC3242304  PMID: 21956448
MeCP2; monoamine transporters; signal transduction; dopamine; serotonin; nucleus accumbens; dopamine; serotonin; neuropharmacology; signal transduction; MeCP2; monoamine transporters; nucleus accumbens
14.  Clinical Presentations, Antiplatelet Strategies and Prognosis of Patients with Stent Thrombosis: An Observational Study of 140 Patients 
PLoS ONE  2012;7(10):e48520.
Background
Until now there has been scarce evidence regarding an optimal antiplatelet strategy and clinical outcomes for patients who had suffered from stent thrombosis (ST).
Methods and Results
140 patients who suffered from stent thrombosis were prospectively registered. Patients received dual (aspirin and 150 mg clopidogrel, N = 66) or triple (additional cilostazol, N = 74) antiplatelet therapy at the physician’s discretion. Thereafter platelet reactivity and one year clinical outcomes were analyzed. The primary outcome included the composite of cardiac death, non-fatal myocardial infarction (MI) or stroke at one year,which developed in 41 (29.3%) patients, consisting of 31 (22.1%) cardiac death, 9 (6.4%) non-fatal MI and 1 (1.4%) stroke. Recurrent definite and probable ST according to ARC definition was observed in 8 (5.7%) and 14 (10.0%) patients, respectively. Triple therapy was associated with significantly lower platelet reactivities (50.2±17.8, % vs. 59.6±17.2, %, P = 0.002) compared to high dose dual antiplatelet therapy. However, the incidence of primary events (24.3% vs. 34.8%, P = 0.172) did not differ between triple and dual antiplatelet therapies. High on-treatment platelet reactivity (HR: 8.35, 95% CI: 2.234∼30.867, P = 0.002) and diabetes (HR: 3.732, 95% CI: 1.353∼10.298, P = 0.011) were independent predictors of primary events.
Conclusions
Patients who suffered from stent thrombosis have a poor prognosis even after revascularization with intensive antiplatelet therapy. Triple antiplatelet therapy was more effective in reducing on-treatment platelet reactivity, compared to high dose dual antiplatelet therapy.
doi:10.1371/journal.pone.0048520
PMCID: PMC3485366  PMID: 23119044
15.  Maternal Mortality in Henan Province, China: Changes between 1996 and 2009 
PLoS ONE  2012;7(10):e47153.
Background
Maternal deaths occur mostly in developing countries and the majority of them are preventable. This study analyzes changes in maternal mortality and related causes in Henan Province, China, between 1996 and 2009, in an attempt to provide a reliable basis for introducing effective interventions to reduce the maternal mortality ratio (MMR), part of the fifth Millennium Development Goal.
Methods and Findings
This population-based maternal mortality survey in Henan Province was carried out from 1996 to 2009. Basic information was obtained from the health care network for women and children and the vital statistics system, from specially trained monitoring personnel in 25 selected monitoring sites and by household survey in each case of maternal death. This data was subsequently reported to the Henan Provincial Maternal and Child Healthcare Hospital. The total MMR in Henan Province declined by 78.4%, from 80.1 per 100 000 live births in 1996 to 17.3 per 100 000 live births in 2009. The decline was more pronounced in rural than in urban areas. The most common causes of maternal death during this period were obstetric hemorrhage (43.8%), pregnancy-induced hypertension (15.8%), amniotic fluid embolism (13.9%) and heart disease (8.0%). The MMR was higher in rural areas with lower income, less education and poorer health care.
Conclusion
There was a remarkable decrease in the MMR in Henan Province between 1996 and 2009 mainly in the rural areas and MMR due to direct obstetric causes such as obstetric hemorrhage. This study indicates that improving the health care network for women, training of obstetric staff at basic-level units, promoting maternal education, and increasing household income are important interventional strategies to reduce the MMR further.
doi:10.1371/journal.pone.0047153
PMCID: PMC3470574  PMID: 23071740
16.  Genome Sequencing of Five Shewanella baltica Strains Recovered from the Oxic-Anoxic Interface of the Baltic Sea 
Journal of Bacteriology  2012;194(5):1236.
Here we describe five Shewanella baltica genomes recovered from the same sample, as well as 12 years apart from the same sampling station. These genomes expand the collection of previously sequenced S. baltica strains and represent a valuable resource for assessing the role of environmental settings on genome adaptation.
doi:10.1128/JB.06468-11
PMCID: PMC3294791  PMID: 22328742
17.  Value of soluble TREM-1, procalcitonin, and C-reactive protein serum levels as biomarkers for detecting bacteremia among sepsis patients with new fever in intensive care units: a prospective cohort study 
BMC Infectious Diseases  2012;12:157.
Background
The purpose of this study was to explore the diagnostic value of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), procalcitonin (PCT), and C-reactive protein (CRP) serum levels for differentiating sepsis from SIRS, identifying new fever caused by bacteremia, and assessing prognosis when new fever occurred.
Methods
We enrolled 144 intensive care unit (ICU) patients: 60 with systemic inflammatory response syndrome (SIRS) and 84 with sepsis complicated by new fever at more than 48 h after ICU admission. Serum sTREM-1, PCT, and CRP levels were measured on the day of admission and at the occurrence of new fever (>38.3°C) during hospitalization. Based on the blood culture results, the patients were divided into a blood culture-positive bacteremia group (33 patients) and blood culture-negative group (51 patients). Based on 28-day survival, all patients, both blood culture-positive and -negative, were further divided into survivor and nonsurvivor groups.
Results
On ICU day 1, the sepsis group had higher serum sTREM-1, PCT, and CRP levels compared with the SIRS group (P <0.05). The areas under the curve (AUC) for these indicators were 0.868 (95% CI, 0.798–0.938), 0.729 (95% CI, 0.637–0.821), and 0.679 (95% CI, 0.578–0.771), respectively. With 108.9 pg/ml as the cut-off point for serum sTREM-1, sensitivity was 0.83 and specificity was 0.81. There was no statistically significant difference in serum sTREM-1 or PCT levels between the blood culture-positive and -negative bacteremia groups with ICU-acquired new fever. However, the nonsurvivors in the blood culture-positive bacteremia group had higher levels of serum sTREM-1 and PCT (P <0.05), with a prognostic AUC for serum sTREM-1 of 0.868 (95% CI, 0.740–0.997).
Conclusions
Serum sTREM-1, PCT, and CRP levels each have a role in the early diagnosis of sepsis. Serum sTREM-1, with the highest sensitivity and specificity of all indicators studied, is especially notable. sTREM-1, PCT, and CRP levels are of no use in determining new fever caused by bacteremia in ICU patients, but sTREM-1 levels reflect the prognosis of bacteremia.
Trial registration
ClinicalTrial.gov identifier NCT01410578
doi:10.1186/1471-2334-12-157
PMCID: PMC3426475  PMID: 22809118
Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1); Fever; Sepsis; Bacteremia; Diagnosis; Prognosis
18.  Genome-wide Regulation of 5hmC, 5mC and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells 
Molecular cell  2011;42(4):451-464.
SUMMARY
DNA methylation at the 5-position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes. The Ten-eleven translocation (Tet) family of 5mC-hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), offers a way for dynamic regulation of DNA methylation. Here we report that Tet1 binds unmodified C, 5mC- or 5hmC-modified CpG-rich DNA through its CXXC domain. Genome-wide mapping of Tet1 and 5hmC reveals mechanisms by which Tet1 controls 5hmC and 5mC levels in mouse embryonic stem cells (mESCs). We also uncover a comprehensive gene network influenced by Tet1. Collectively, our data suggest that Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting 5mC to 5hmC through hydroxylase activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development.
doi:10.1016/j.molcel.2011.04.005
PMCID: PMC3099128  PMID: 21514197
20.  tert-Butyl 6-amino-5-cyano-2-(2-meth­oxy­eth­yl)nicotinate 
The title compound, C14H19N3O3, was synthesized by the reaction of 3-meth­oxy­propionitrile, tert-butyl bromo­acetate and eth­oxy­methyl­enemalononitrile. In the crystal, N—H⋯O hydrogen bonds link the mol­ecules into chains propagating along the b axis.
doi:10.1107/S1600536812014328
PMCID: PMC3381644  PMID: 22737103
21.  The Characteristics of Blood Glucose and WBC Counts in Peripheral Blood of Cases of Hand Foot and Mouth Disease in China: A Systematic Review 
PLoS ONE  2012;7(1):e29003.
Background
Outbreaks of Hand Foot and Mouth Disease (HFMD) have occurred in many parts of the world especially in China. We aimed to summarize the characteristics of the levels of blood glucose and white blood cell (WBC) counts in cases of HFMD in Mainland China and Taiwan, using meta-analysis based on systematic review of published articles.
Methods
We systematically reviewed published studies, from the MEDLINE and WANFANG Data, about the levels of blood glucose and WBC counts in cases of HFMD until 15th June 2011, and quantitatively summarized the characteristics of them using meta-analysis.
Results
In total, 37 studies were included in this review. In Mainland China and Taiwan, generally, the average level of blood glucose, the prevalence of hyperglycemia, WBC counts and the prevalence of leukocytosis increased with the severity of the illness. There was no significant difference in the prevalence of leukocytosis between ANS (autonomic nervous system dysregulation)/PE (pulmonary edema) group and CNS (central nervous system) group, and in the average level of blood glucose between healthy controls and mild cases of HFMD. WBC counts in cases infected by EV71 were less than those in cases infected by CA16.
Conclusions
our analyses indicated that blood glucose and WBC counts increased with the severity of HFMD disease, which would help doctors to manage patients efficiently.
doi:10.1371/journal.pone.0029003
PMCID: PMC3250408  PMID: 22235257
22.  Unprecedented levels of horizontal gene transfer among spatially co-occurring Shewanella bacteria from the Baltic Sea 
The ISME journal  2010;5(1):131-140.
High-throughput sequencing studies during the last decade have uncovered that bacterial genomes are very diverse and dynamic, resulting primarily from the frequent and promiscuous horizontal gene exchange that characterizes the bacterial domain of life. However, a robust understanding of the rates of genetic exchange for most bacterial species under natural conditions and the influence of the ecological settings on the rates remain elusive, severely limiting our view of the microbial world. Here, we analyzed the complete genomic sequences and expressed transcriptomes of several Shewanella baltica isolates recovered from different depths in the Baltic Sea and found that isolates from more similar depths had exchanged a larger fraction of their core and auxiliary genome, up to 20% of the total, compared with isolates from more different depths. The exchanged genes seem to be ecologically important and contribute to the successful adaptation of the isolates to the unique physicochemical conditions of the depth. Importantly, the latter genes were exchanged in very recent past, presumably as an effect of isolate's seasonal migration across the water column, and reflected sexual speciation within the same depth. Therefore, our findings reveal that genetic exchange in response to environmental settings may be surprisingly rapid, which has important broader impacts for understanding bacterial speciation and evolution and for modeling bacterial responses to human-induced environmental impacts.
doi:10.1038/ismej.2010.93
PMCID: PMC3105679  PMID: 20596068
comparative genomics; genome evolution; speciation; horizontal gene transfer; recombination; Shewanella baltica
23.  Advanced Pneumatic Therapy in Self-Care of Chronic Lymphedema of the Trunk 
Lymphatic Research and Biology  2010;8(4):209-215.
Abstract
Background
The purpose of this study was to conduct a preliminary, post-market, home study of the Flexitouch® system to examine the potential efficacy of the device as a component of self-care in breast cancer survivors with truncal lymphedema.
Methods and Results
A quasi-experimental, pre-treatment, post-treatment design was used. Twelve participants received a total of ten self-administered, consecutive, one hour per day treatments. Treatments one and two were observed by study staff and the remaining eight were unobserved. Assessments were conducted at baseline, after the first two treatments, mid-way through therapy, and at the end-of-study. Logs revealed 100% compliance with the eight prescribed unobserved home treatments. Symptoms were assessed by self-report symptom surveys. Signs, objectively observed physical phenomenon, were assessed by staff-initiated skin examination and circumferential truncal measurements. Statistically significant improvement in truncal symptoms and sleep were found. Changes in function and girth were not statistically significant in this initial study.
Conclusions
Breast cancer survivors with truncal lymphedema may benefit from using an advanced pneumatic compression devices with truncal treatment as part of their self-care program. Participants were highly compliant in device use. Further research of this intervention is warranted. To facilitate future research, clinically meaningful reductions in truncal girth should be defined.
doi:10.1089/lrb.2010.0010
PMCID: PMC3008167  PMID: 21190493
24.  Comparing Enterovirus 71 with Coxsackievirus A16 by analyzing nucleotide sequences and antigenicity of recombinant proteins of VP1s and VP4s 
BMC Microbiology  2011;11:246.
Background
Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are two major etiological agents of Hand, Foot and Mouth Disease (HFMD). EV71 is associated with severe cases but not CA16. The mechanisms contributed to the different pathogenesis of these two viruses are unknown. VP1 and VP4 are two major structural proteins of these viruses, and should be paid close attention to.
Results
The sequences of vp1s from 14 EV71 and 14 CA16, and vp4s from 10 EV71 and 1 CA16 isolated in this study during 2007 to 2009 HFMD seasons were analyzed together with the corresponding sequences available in GenBank using DNAStar and MEGA 4.0. Phylogenetic analysis of complete vp1s or vp4s showed that EV71 isolated in Beijing belonged to C4 and CA16 belonged to lineage B2 (lineage C). VP1s and VP4s from 4 strains of viruses expressed in E. coli BL21 cells were used to detect IgM and IgG in human sera by Western Blot. The detection of IgM against VP1s of EV71 and CA16 showed consistent results with current infection, while none of the sera were positive against VP4s of EV71 and CA16. There was significant difference in the positive rates between EV71 VP1 and CA16 VP1 (χ2 = 5.02, P < 0.05) as well as EV71 VP4 and CA16 VP4 (χ2 = 15.30, P < 0.01) in the detection of IgG against recombinant proteins with same batch of serum samples. The sera-positive rate of IgG against VP1 was higher than that against VP4 for both EV71 (χ2 = 26.47, P < 0.01) and CA16 (χ2 = 16.78, P < 0.01), which might be because of different positions of VP1 and VP4 in the capsid of the viruses.
Conclusions
EV71 and CA16 were highly diverse in the nucleotide sequences of vp1s and vp4s. The sera positive rates of VP1 and VP4 of EV71 were lower than those of CA16 respectively, which suggested a less exposure rate to EV71 than CA16 in Beijing population. Human serum antibodies detected by Western blot using VP1s and VP4s as antigen indicated that the immunological reaction to VP1 and VP4 of both EV71 and CA16 was different.
doi:10.1186/1471-2180-11-246
PMCID: PMC3217892  PMID: 22050722
25.  Targeted Single-Shot Methods for Diffusion-Weighted Imaging in the Kidneys 
Purpose
To investigate the feasibility of combining the inner-volume-imaging (IVI) technique with single-shot diffusion-weighted (DW) spin-echo echo-planar imaging (SE-EPI) and DW-SPLICE (split acquisition of fast spin-echo) sequences for renal DW imaging.
Materials and Methods
Renal DW imaging was performed in 10 healthy volunteers using single-shot DW-SE-EPI, DW-SPLICE, targeted-DW-SE-EPI and targeted-DW-SPLICE. We compared the quantitative diffusion measurement accuracy and image quality of these targeted-DW-SE-EPI and targeted DW-SPLICE methods with conventional full FOV DW-SE-EPI and DW-SPLICE measurements in phantoms and normal volunteers.
Results
Compared with full FOV DW-SE-EPI and DW-SPLICE methods, targeted-DW-SE-EPI and targeted-DW-SPLICE approaches produced images of superior overall quality with fewer artifacts, less distortion and reduced spatial blurring in both phantom and volunteer studies. The ADC values measured with each of the four methods were similar and in agreement with previously published data. There were no statistically significant differences between the ADC values and intra-voxel incoherent motion (IVIM) measurements in the kidney cortex and medulla using single-shot DW-SE-EPI, targeted-DW-EPI and targeted-DW-SPLICE (p > 0.05).
Conclusion
Compared with full-FOV DW imaging methods, targeted-DW-SE-EPI and targeted-DW-SPLICE techniques reduced image distortion and artifacts observed in the single-shot DW-SE-EPI images, reduced blurring in DW-SPLICE images and produced comparable quantitative DW and IVIM measurements to those produced with conventional full-FOV approaches.
doi:10.1002/jmri.22556
PMCID: PMC3157974  PMID: 21591023
renal; diffusion; targeted; inner volume imaging; SPLICE; EPI

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