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1.  Clinical practice guidelines for hypertension in China: a systematic review of the methodological quality 
BMJ Open  2015;5(7):e008099.
Objective
Clinical practice guidelines (CPGs) provide clinicians with specific recommendations for practice, but due to the increasing number of CPGs developed by diverse organisations over the past few years, there are concerns about the quality of some CPGs. This paper proposes a systematic review of the methodological quality of the CPGs for hypertension that were developed in China.
Design
A systematic review of CPGs for the management of hypertension in adult patients in China.
Data resources
Chinese electronic databases, Chinese guideline websites and Google Scholar were searched, and the reference lists of relevant publications were also screened for additional information. CPGs for the management of hypertension in adult patients were identified. The main characteristics of the CPGs were extracted, and the scaled Appraisal of Guidelines, REsearch and Evaluation II (AGREE II) domain percentages were independently evaluated by two reviewers.
Results
A total of 17 CPGs, with publication dates ranging from 2001 to 2011, were identified. There was considerable variation in the quality of the CPGs across the AGREE II domains. Overall, the domains of ‘rigor of development’ and ‘editorial independence’ were poorly addressed, with an average score of 18% and 16%, respectively. Also less well addressed were the ‘stakeholder involvement’ and ‘applicability’ domains, for which the average domain scores were 28% and 20%, respectively. The CPGs performance was less problematic in the domains of ‘scope and purpose’ and ‘clarity and presentation’, with a median of 41% for both. After considering the domain scores, 8 CPGs could be recommended with modification for use.
Conclusions
There is considerable room for improvement of the methodological quality of CPGs for hypertension in China. Greater efforts should to be devoted to ensure the explicit and transparent reporting of potential conflicts of interest of stakeholders, and to consider the quality of the evidence and grade recommendations in the CPG development process.
doi:10.1136/bmjopen-2015-008099
PMCID: PMC4513449  PMID: 26179649
2.  Forward genetic screen for auxin-deficient mutants by cytokinin 
Scientific Reports  2015;5:11923.
Identification of mutants with impairments in auxin biosynthesis and dynamics by forward genetic screening is hindered by the complexity, redundancy and necessity of the pathways involved. Furthermore, although a few auxin-deficient mutants have been recently identified by screening for altered responses to shade, ethylene, N-1-naphthylphthalamic acid (NPA) or cytokinin (CK), there is still a lack of robust markers for systematically isolating such mutants. We hypothesized that a potentially suitable phenotypic marker is root curling induced by CK, as observed in the auxin biosynthesis mutant CK-induced root curling 1 / tryptophan aminotransferase of Arabidopsis 1 (ckrc1/taa1). Phenotypic observations, genetic analyses and biochemical complementation tests of Arabidopsis seedlings displaying the trait in large-scale genetic screens showed that it can facilitate isolation of mutants with perturbations in auxin biosynthesis, transport and signaling. However, unlike transport/signaling mutants, the curled (or wavy) root phenotypes of auxin-deficient mutants were significantly induced by CKs and could be rescued by exogenous auxins. Mutants allelic to several known auxin biosynthesis mutants were re-isolated, but several new classes of auxin-deficient mutants were also isolated. The findings show that CK-induced root curling provides an effective marker for discovering genes involved in auxin biosynthesis or homeostasis.
doi:10.1038/srep11923
PMCID: PMC4491711  PMID: 26143750
3.  Biofumigation on Post-Harvest Diseases of Fruits Using a New Volatile-Producing Fungus of Ceratocystis fimbriata 
PLoS ONE  2015;10(7):e0132009.
A variety of volatile organic compounds (VOCs) produced by Ceratocystis fimbriata have strong bioactivity against a wide range of fungi, bacteria and oomycetes. Mycelial growth, conidial production, and spore germination of fungi and oomycetes were significantly inhibited after exposure to cultures of C. fimbriata, and colony formation of bacteria was also inhibited. Two post-harvest diseases, peach brown rot caused by Monilinia fructicola and citrus green mold caused by Penicillium digitatum, were controlled during a 4-day storage by enclosing wound-inoculated fruits with 10 standard diameter Petri plate cultures of C. fimbriata in a 15 L box. The fruits were freshly inoculated at onset of storage and the cultures of C. fimbriata were 6 days old. Percentage of control was 92 and 97%, respectively. After exposure to C. fimbriata VOCs, severely misshapen hyphae and conidia of these two post-harvest pathogens were observed by scanning electron microscopy, and their pathogenicity was lost or greatly reduced.
doi:10.1371/journal.pone.0132009
PMCID: PMC4492557  PMID: 26147922
4.  Acaricidal activity of extracts from Ligularia virgaurea against the Sarcoptes scabiei mite in vitro 
The aim of the present study was to investigate the acaricidal activity of Ligularia virgaurea. An extract was prepared by refluxing with ethanol and steam distillation, and its toxic effect was tested in vitro against Sarcoptes scabiei. The data from the toxicity tests were analyzed using a complementary log-log (CLL) model. The ethanol extract exhibited strong acaricidal activity against these mites; at a concentration of 2 g/ml it killed all S. scabiei within 2 h and at 1 g/ml it killed all S. scabiei within 6 h. Similarly, 2, 1, 0.5 and 0.25 g/ml concentrations of the extract had strong toxicity against S. scabiei, with median lethal time (LT50) values of 0.716, 1.741, 2.968 and 4.838 h, respectively. The median lethal concentration (LC50) values were 1.388, 0.624, 0.310 and 0.213 g/ml for Scabies mite in 1, 2, 4 and 6 h, respectively. The results indicate that the L. virgaurea extract has strong acaricidal activity and may be exploited as a novel treatment for the effective control of acariasis in animals.
doi:10.3892/etm.2015.2503
PMCID: PMC4487052  PMID: 26170943
acaricidal activity; Ligularia virgaurea; Sarcoptes scabiei; toxic effect
5.  Frequent problems and their resolutions by using thermal asymmetric interlaced PCR (TAIL-PCR) to clone genes in Arabidopsis T-DNA tagged mutants 
T-DNA insertional mutagenesis is a powerful tool in Arabidopsis functional genomics research. Previous studies have developed thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR) as an efficient strategy in isolation of DNA sequences adjacent to known sequences in T-DNA tagged mutants. However, a number of problems are encountered when attempts are made to clone flanking sequences in T-DNA tagged mutants. Therefore, it is necessary to improve the efficiency of cloning mutagenesis. Here, we present the most frequent problems and provide an improved method to increase TAIL-PCR efficiency. Even then, it is not always possible to successfully obtain flanking sequences; in such cases, we recommend using high-throughput sequencing to determine the mutations.
doi:10.1080/13102818.2014.998161
PMCID: PMC4433792  PMID: 26019639
TAIL-PCR; T-DNA tagged mutants; complex T-DNA insertion; high-throughput sequencing
6.  Phylogenetic and Taxonomic Revision of an Enigmatic Group of Haptorian Ciliates, with Establishment of the Kentrophyllidae fam. n. (Protozoa, Ciliophora, Litostomatea, Pleurostomatida) 
PLoS ONE  2015;10(5):e0123720.
Haptorian ciliates in the closely similar genera Kentrophyllum and Epiphyllum possess a unique pattern of ciliature and are distinguished from one another only by the presence or absence of cytoplasmic spines projecting from the margin of the cell. Phylogenetic analyses based on SSU rDNA sequences of three new samples from coastal habitats in China revealed that species in the two genera clustered together indiscriminately (i.e. forms of neither genus clustered into an independent clade) as a maximally supported, monophyletic clade that branches basally to all other clades in the order Pleurostomatida and is strongly divergent from other members of the family in which the genera have been placed. As a result, we propose that Epiphyllum be synonymized with Kentrophyllum and that a new family Kentrophyllidae fam. n. be established for the genus. We hypothesize that the two-sutures of Kentrophyllum is a plesiomorphy within the Pleurostomatida and the unique peripheral kinety might represent an autapomorphy of Kentrophyllum. In addition, we provide a taxonomic revision of Kentrophyllum including description of three new species (K. bispinum sp. n., K. strumosum sp. n., and K. qingdaoense sp. n.), redescription of K. verrucosum (Stokes, 1893) Petz et al., 1995, and three new combinations (K. soliforme (Fauré-Fremiet, 1908) comb. n., K. hohuensis (Wang and Nie, 1933) comb. n. and K. shenzhenense (Pan et al., 2010) comb. n.). The surface ultrastructure of the genus Kentrophyllum is recorded for the first time. And a key to all known species of Kentrophyllum was also suggested.
doi:10.1371/journal.pone.0123720
PMCID: PMC4422516  PMID: 25946216
7.  The effect of a very brief smoking-reduction intervention in smokers who have no intention to quit: Study protocol for a randomized controlled trial 
BMC Public Health  2015;15:418.
Background
Tobacco use is one of the most common preventable causes of death, but more than half of the Chinese men still use tobacco products. Moreover, 63.6% of Chinese smokers have stated that they would not consider quitting. Specialized and intensive smoking-cessation services are too expensive and passive to have major clinical and public health impacts in developing countries like China. Smoking cessation medications are not covered by medical insurance, and their high price prevents Chinese smokers from using them. Brief interventions are needed to provide cost-effective and timesaving tobacco dependence treatments in China mainland.
Methods/design
We describe a two-arm randomized controlled trial for smokers who have no intention to quit. The project will be conducted in outpatient clinics at a large hospital in Beijing, China. Both arms include one face-to-face interview plus five follow-up interventions. Each intervention will last approximately one minute. Subjects allocated to the smoking-reduction intervention arm (SRI) will be advised to reduce smoking consumption to at least half of their current consumption level within the next month. All subjects in the SRI will be warned to bear in mind that an attempt to reduce smoking is an intermediate step before complete cessation. Smokers who have successfully reduced their smoking consumption will be encouraged to completely cease smoking. Controls are subjects allocated to the exercise- and diet-advice arm (EDA) and will be given advice about healthy diet and physical activity, but the advice will not include smoking cessation or reduction. Data collection will be done at baseline and at each follow-up interview using standardized questionnaires. The primary outcomes include self-reported and biochemically verified 7-day point prevalence and prolonged abstinence rates at 12-month follow-up.
Discussion
We expect that an intention to quit in smoking outpatients can be motivated by physicians in the clinic setting. If this very brief smoking-reduction intervention can be demonstrated to have a positive impact on long-term smoking cessation, this strategy has the potential to be a viable and acceptable approach and may be used widely in China and elsewhere.
Clinical trial registration
ClinicalTrials.gov: NCT02370147 (date of registration: 23th February, 2015).
doi:10.1186/s12889-015-1749-7
PMCID: PMC4443634  PMID: 25944023
Very brief counseling; Smoking-reduction intervention; No intention to quit; Randomized controlled trial; Telephone follow-up
8.  Safety of Chinese Herbal Medicine for Chronic Obstructive Pulmonary Disease 
Chinese herbal medicine (CHM) is increasingly used by patients with chronic obstructive pulmonary disease (COPD); however, there has been no systematic evaluation of its safety. This review examined the adverse events (AEs) reported in clinical studies of CHM for COPD. Five English databases (PubMed, Embase, CINAHL, AMED, and CENTRAL) and four Chinese databases (CBM, CNKI, CQVIP, and Wanfang Data) were searched from inception to May 2013. Adverse event data, including nature, severity, author-assigned causality, management, and outcome, were extracted from included studies. Descriptive statistics were used for the rate of adverse events. Of the 152 included studies, AEs were reported in 47 studies. The rate of adverse events was slightly lower in the CHM groups compared with controls (84 events in 5,909 participants, 1.4% versus 102 events in 5,676 participants, 1.8%). The most frequently reported adverse event was nausea (28 cases in the CHM groups and 19 cases in the control groups), which was more common in studies where CHM was combined with pharmacotherapy to treat acute exacerbation of COPD. Other frequent adverse events were abdominal discomfort, dry mouth, and dizziness. Detailed information about the adverse events was scant. Overall, CHM appears to be well tolerated in people with COPD.
doi:10.1155/2015/380678
PMCID: PMC4391162  PMID: 25883670
9.  Functional Roles of Three Cutin Biosynthetic Acyltransferases in Cytokinin Responses and Skotomorphogenesis 
PLoS ONE  2015;10(3):e0121943.
Cytokinins (CKs) regulate plant development and growth via a two-component signaling pathway. By forward genetic screening, we isolated an Arabidopsis mutant named grow fast on cytokinins 1 (gfc1), whose seedlings grew larger aerial parts on MS medium with CK. gfc1 is allelic to a previously reported cutin mutant defective in cuticular ridges (dcr). GFC1/DCR encodes a soluble BAHD acyltransferase (a name based on the first four enzymes characterized in this family: Benzylalcohol O-acetyltransferase, Anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase and Deacetylvindoline 4-O-acetyltransferase) with diacylglycerol acyltransferase (DGAT) activity in vitro and is necessary for normal cuticle formation on epidermis in vivo. Here we show that gfc1 was a CK-insensitive mutant, as revealed by its low regeneration frequency in vitro and resistance to CK in adventitious root formation and dark-grown hypocotyl inhibition assays. In addition, gfc1 had de-etiolated phenotypes in darkness and was therefore defective in skotomorphogenesis. The background expression levels of most type-A Arabidopsis Response Regulator (ARR) genes were higher in the gfc1 mutant. The gfc1-associated phenotypes were also observed in the cutin-deficient glycerol-3-phosphate acyltransferase 4/8 (gpat4/8) double mutant [defective in glycerol-3-phosphate (G3P) acyltransferase enzymes GPAT4 and GPAT8, which redundantly catalyze the acylation of G3P by hydroxyl fatty acid (OH-FA)], but not in the cutin-deficient mutant cytochrome p450, family 86, subfamily A, polypeptide 2/aberrant induction of type three 1 (cyp86A2/att1), which affects the biosynthesis of some OH-FAs. Our results indicate that some acyltransferases associated with cutin formation are involved in CK responses and skotomorphogenesis in Arabidopsis.
doi:10.1371/journal.pone.0121943
PMCID: PMC4372371  PMID: 25803274
10.  MiR-21 promotes intrahepatic cholangiocarcinoma proliferation and growth in vitro and in vivo by targeting PTPN14 and PTEN 
Oncotarget  2015;6(8):5932-5946.
Intrahepatic cholangiocarcinoma (ICC) constitutes the second-most common primary hepatic malignancy. MicroRNAs (miRNAs) play important roles in the pathogenesis of ICC. However, the clinical significance of miR-21 levels in ICC remains unclear. Here, we investigated the role of miR-21 in ICC and found that its expression was significantly upregulated in serum of ICC patients. Serum miR-21 levels robustly distinguished ICC patients from control subjects. Further experiments showed that inhibition of miR-21 suppressed ICC cell proliferation in vitro and tumor growth in vivo. Specifically, inhibition of miR-21 induced cell cycle arrest and apoptosis. Moreover, PTPN14 and PTEN were identified as direct and functional targets of miR-21. Finally, we showed high expression levels of miR-21 were closely related to adverse clinical features, diminished survival, and poor prognosis in ICC patients. This study revealed functional and mechanistic links between miR-21 and tumor suppressor genes, PTPN14 and PTEN, in the pathogenesis of ICC. MiR-21 not only plays important roles in the regulation of cell proliferation and tumor growth in ICC, but is also a diagnostic and prognostic marker, and a potential therapeutic target for ICC.
PMCID: PMC4467412  PMID: 25803229
Intrahepatic cholangiocarcinoma; miR-21; PTPN14; PTEN; tumorigenesis
11.  Changes in and Patterns of Smoking Exposure in an Elderly Urban Population in Beijing: 2001–2010 
PLoS ONE  2015;10(3):e0118500.
Objective
The study aims to explore the patterns and changes of active and passive smoking in the elderly population.
Methods
Two cross-sectional surveys with representative samples of urban populations, aged between 60 and 95 years old, were conducted in 2001 and 2010 in Beijing. A current smoker was defined as a person who smoked a tobacco product at the time of the survey, and a passive smoker was defined as a person who had been exposed to smoke exhaled by a smoker for more than 15 minutes per day more than once per week.
Results
A total of 2,277 participants in 2001 and 2,102 participants in 2010 completed the survey. The current smoking prevalence changed slightly in males (24.7 vs. 21.2%, P = 0.081), while the prevalence in females decreased significantly from 8.8% (95% CI: 7.3–10.3%) in 2001 to 4.1% (95% CI: 3.0–5.2%) in 2010 (P<0.001). The prevalence of passive smoking was 30.5% (95% CI: 28.6–32.4%) in 2001 and 30.0% (95% CI: 28.1–32.0%) in 2010. The main source of secondhand smoke switched from a spouse in 2001 to offspring in 2010. This trend was observed in both sexes. Passive smoking in males from a smoking spouse decreased from 5.7% to 2.4% (P<0.001), while that from smoking offspring increased from 7.3 to 14.5% (P<0.001). Passive smoking in females from a spouse decreased from 30.6 to 17.6%, while that from offspring increased from 5.3 to 15.4% (P<0.001).
Conclusion
Offspring became the main source of secondhand smoke for the elderly. Our findings demonstrated the importance of implementing smoking prevention programs, to educate older adults who live with a smoking spouse and/or offspring.
doi:10.1371/journal.pone.0118500
PMCID: PMC4364981  PMID: 25785722
12.  Effects of dexmedetomidine on cellular immunity of perioperative period in children with brain neoplasms 
Objective: To study the effects of dexmedetomidine (Dex) on cellular immunity during the perioperative period in children with brain neoplasms. Methods: Forty children with brain neoplasms scheduled for selective operation were recruited and divided randomly into two groups. The Dex group was given a loading dose of 1 μg*kg-1 Dex 15 minutes before anesthesia induction followed by a continuous infusion of 0.5 μg × kg-1 × h-1 Dex. Patients in control group received a same volume of normal saline for a same time period. Venous blood was collected before anesthesia (T0), 1 h after operation started (T1), immediately after operation ended (T2), 1 day after operation (T3) and 3 days after operation (T4), respectively. Results: CD3 +, CD4 +, CD4 +/CD8 +, NK and B cells at T1-T3 decreased significantly (P < 0.05) in both groups compared with those at T0, while the decrease of CD3 +, CD4 +, CD4 +/CD8 + and NK cells at T1-T3 and B cells at T1-T2 in Dex group was significantly less than the control group (P < 0.05). All values at T4 recovered to the level before anesthesia in both groups. Conclusion: Dex given by a continuous intravenous infusion during general anesthesia may effectively inhibit the stress responses and reduce the inhibition of cellular immunity in children with brain neoplasms during the perioperative period.
PMCID: PMC4402876  PMID: 25932229
Dexmedetomidine; brain neoplasms; T lymphocyte; NK cells; B lymphocyte
13.  Postconditioning with simvastatin decreases myocardial injury in rats following acute myocardial ischemia 
The aim of the present study was to investigate whether postconditioning with simvastatin attenuated myocardial ischemia reperfusion injury by inhibiting the expression of high mobility group box 1 (HMGB1) in rat myocardium following acute myocardial ischemia. In total, 30 male Sprague-Dawley rats were divided into sham operation (sham; n=10), acute myocardial infarction (AMI; n=10) and simvastatin (sim; n=10) groups. The AMI and sim groups were subjected to ischemia for 30 min, followed by reperfusion for 180 min. The rats in the sim group were administered 20 mg/kg simvastatin intravenously 5 min prior to reperfusion. Subsequently, the infarct size, serum cardiac troponin (c-TnI), tumor necrosis factor (TNF)-α and myocardial malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. Western blot analysis was used to detect the protein expression of HMGB1. Postconditioning with simvastatin was shown to decrease the infarct size and HMGB1 expression levels in the myocardium following AMI (P<0.05). In addition, postconditioning with simvastatin not only decreased the serum levels of c-TnI and TNF-α (P<0.05), but also inhibited the increase in MDA levels and the reduction in SOD activity (P<0.05). Therefore, postconditioning with simvastatin was shown to attenuate myocardial injury. The underlying mechanism may be associated with the downregulation of HMGB1 expression in the ischemic myocardium.
doi:10.3892/etm.2015.2273
PMCID: PMC4353796  PMID: 25780404
simvastatin; acute myocardial infarction; postconditioning; high mobility group box 1
14.  An Efficient Strategy for Heterologous Expression and Purification of Active Peptide Hainantoxin-IV 
PLoS ONE  2015;10(2):e0117099.
Hainantoxin-IV (HNTX-IV) from the venom of the spider Selenocosmia hainana is a potent antagonist that specifically inhibits the tetrodotoxin-sensitive (TTX-S) sodium channels. The toxin peptide consists of 35 amino acids and adopts a typical inhibitory cystine knot (ICK) motif. To obtain adequate HNTX-IV peptides for further insight into the structure-activity relationships of the toxin, a novel strategy including cloning, expression and purification was developed in an E. coli expression system. For this purpose, a seamless restriction-free (RF) cloning method was employed for the construction of an expression vector to avoid introducing unwanted sequences into the target gene. Furthermore, the solubility of recombinant HNTX-IV could be promoted efficiently by the combination of a glutathione S-transferase (GST) tag and a small ubiquitin-related modifier (SUMO) tag. Finally, an affinity-chromatography-free purification strategy was developed by cut-off dialysis tubing combined with trichloroacetic acid (TCA) extraction. Further HPLC purification yielded recombinant, tag-free HNTX-IV with high yield and purity. The molecular weight of recombinant HNTX-IV (rHNTX-IV) is identical to its theoretical value according to Matrix-Assisted Laser Desorption / Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) analysis. The recombinant toxin has similar activity (IC50 value of 120 nM) on the tetrodotoxin-sensitive (TTX-S) sodium channels in adult rat dorsal root ganglion (DRG) neurons to native toxins. In the report, an efficient and cost-effective strategy for producing rHNTX-IV was developed, which paved the way for the further study of structure-activity relationships of rHNTX-IV and its pharmaceutical applications.
doi:10.1371/journal.pone.0117099
PMCID: PMC4315428  PMID: 25647561
15.  Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy 
The Journal of Experimental Medicine  2014;211(7):1449-1464.
IL-17A stimulates cardiac fibroblasts to produce inflammatory mediators critical for the recruitment and differentiation of myeloid cells during inflammatory dilated cardiomyopathy.
Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in individuals below the age of 40. We recently reported that IL-17A is required for the development of DCMi. We show a novel pathway connecting IL-17A, cardiac fibroblasts (CFs), GM-CSF, and heart-infiltrating myeloid cells with the pathogenesis of DCMi. Il17ra−/− mice were protected from DCMi, and this was associated with significantly diminished neutrophil and Ly6Chi monocyte/macrophage (MO/MΦ) cardiac infiltrates. Depletion of Ly6Chi MO/MΦ also protected mice from DCMi. Mechanistically, IL-17A stimulated CFs to produce key chemokines and cytokines that are critical downstream effectors in the recruitment and differentiation of myeloid cells. Moreover, IL-17A directs Ly6Chi MO/MΦ in trans toward a more proinflammatory phenotype via CF-derived GM-CSF. Collectively, this IL-17A–fibroblast–GM-CSF–MO/MΦ axis could provide a novel target for the treatment of DCMi and related inflammatory cardiac diseases.
doi:10.1084/jem.20132126
PMCID: PMC4076595  PMID: 24935258
16.  Twenty-five-year changing pattern of gonococcal antimicrobial susceptibility in Shanghai: surveillance and its impact on treatment guidelines 
BMC Infectious Diseases  2014;14:731.
Background
Antimicrobial resistance of Neisseria gonorrhoeae is a serious health problem in China. Gonococcal antimicrobial susceptibility has been monitored in Shanghai since 1988. In this study, we examined the changing pattern of gonococcal antimicrobial susceptibility based on data from N. gonorrhoeae isolates collected over the past 25 years.
Methods
Approximately 100–200 isolates each year (1988–2013) were tested for their susceptibility to penicillin (PEN), tetracycline (TET), ciprofloxacin (CIP), ceftriaxone (CRO) and spectinomycin (SPT), using the agar dilution method. Plasmid-mediated N. gonorrhoeae antimicrobial resistance, comprising penicillinase-producing N. gonorrhoeae (presumed PPNG) and high-level tetracycline resistance N. gonorrhoeae (presumed TRNG), were also determined. Breakpoints for susceptibilities followed those described by the Clinical and Laboratory Standard Institute and the European Committee on Antimicrobial Susceptibility Testing.
Results
A high proportion of isolates were resistant to PEN, TET and CIP, ranging from less than 20% at the beginning of the survey, increasing in the late 1990s and reaching over 90% in recent years. The proportion of isolates exhibiting plasmid-mediated resistance exceeded 38% for presumed PPNG and 20% for presumed TRNG in recent years. The proportion of CRO nonsusceptible isolates (MIC ≥ 0.125 mg/L) ranged from 7% to 13% in most of the study years. Almost all isolates were susceptible to SPT. The SPT MIC90 was 16–32 mg/L for 2008–2013. The proportion of CRO nonsusceptible-associated multiple-drug-resistant (MDR) isolates was over 5% in most of the study years.
Conclusions
N. gonorrhoeae isolates in Shanghai were resistant to PEN, TET and CIP. Furthermore, CRO nonsusceptible and MDR isolates were prevalent. N. gonorrhoeae isolates were also found to be susceptible to SPT. It is recommended that the CRO dose be increased from currently recommended 250 mg to 500 mg and that SPT be an alternative in treating urogenital gonorrhea. Our findings highlight the importance of both regional and national surveillance programs for the prompt modification of treatment guidelines, vital in responding to the changing pattern of gonococcal antimicrobial susceptibility.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-014-0731-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-014-0731-9
PMCID: PMC4334756  PMID: 25547132
Neisseria gonorrhoeae; Antimicrobial susceptibility; Multiple drug resistance; Ceftriaxone; Spectinomycin
17.  Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN 
British Journal of Haematology  2013;164(1):811-821.
Summary
Cereblon (CRBN), the molecular target of lenalidomide and pomalidomide, is a substrate receptor of the cullin ring E3 ubiquitin ligase complex, CRL4CRBN. T cell co-stimulation by lenalidomide or pomalidomide is cereblon dependent: however, the CRL4CRBN substrates responsible for T cell co-stimulation have yet to be identified. Here we demonstrate that interaction of the transcription factors Ikaros (IKZF1, encoded by the IKZF1 gene) and Aiolos (IKZF3, encoded by the IKZF3 gene) with CRL4CRBN is induced by lenalidomide or pomalidomide. Each agent promotes Aiolos and Ikaros binding to CRL4CRBN with enhanced ubiquitination leading to cereblon-dependent proteosomal degradation in T lymphocytes. We confirm that Aiolos and Ikaros are transcriptional repressors of interleukin-2 expression. The findings link lenalidomide- or pomalidomide-induced degradation of these transcriptional suppressors to well documented T cell activation. Importantly, Aiolos could serve as a proximal pharmacodynamic marker for lenalidomide and pomalidomide, as healthy human subjects administered lenalidomide demonstrated Aiolos degradation in their peripheral T cells. In conclusion, we present a molecular model in which drug binding to cereblon results in the interaction of Ikaros and Aiolos to CRL4CRBN, leading to their ubiquitination, subsequent proteasomal degradation and T cell activation.
doi:10.1111/bjh.12708
PMCID: PMC4232904  PMID: 24328678
lenalidomide; pomalidomide; Cereblon; Ikaros; Aiolos
18.  Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat 
Respiratory Research  2014;15(1):137.
Background
Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.
Methods
An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR.
Results
Maternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.
Conclusions
These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.
doi:10.1186/s12931-014-0137-7
PMCID: PMC4233040  PMID: 25391516
Allergen; Asthma; Epigenetics; Endothelin-1; Intrauterine growth retardation
19.  Clinical evaluation of the Asian proximal femur intramedullary nail antirotation system (PFNA-II) for treatment of intertrochanteric fractures 
Background
The preferred treatment of intertrochanteric fractures in aged patients is controversial. The purpose of the present study was to evaluate the outcomes of the Asian proximal femur intramedullary nail antirotation system (PFNA-II) for stabilization of such fractures.
Methods
The PFNA-II was used to treat intertrochanteric fractures in 163 elderly patients from March 2010 to March 2013. The patients comprised 69 men and 94 women with a mean age of 74.7 ± 13.0 years. All fractures were classified by the Orthopaedic Trauma Association classification system; 53, 83, and 27 fractures were classified as 31A1, 31A2, and 31A3, respectively. We statistically evaluated the intraoperative blood loss, operation time, incision length, X-ray exposure time, and postoperative outcomes. Patients were followed up for a mean of 15.2 months (range, 10–24 months). Functional outcomes were assessed according to the Harris hip scoring system.
Results
Statistical analysis revealed an average operation time of 45.7 min (range, 35–110 min), average intraoperative blood loss of 115.2 mL (range, 65–430 mL), X-ray exposure time of 2.7 ± 1.4 s (range, 2–6 s), and total incision length of 6.5 ± 2.2 cm (range, 5.5–13.0 cm). Patients were followed up for a mean of 14.5 months (range, 10–24 months). The neck shaft angle was 134° ±15° (range, 115°–150°), and the fracture healing time was 14.0 ± 2.5 weeks (range, 11–19 weeks). The Harris hip score was 85.6 ± 17.5 points (range, 65–100 points) and included 41 excellent cases (25.15%), 92 good cases (56.44%), 26 moderate cases (15.95%), and 4 poor cases (2.45%) for a positive outcome rate of 81.60%. There were no varus hip deformities, screw cutouts, or femoral shaft fractures. Fourteen patients had thigh pain (9.82%), and five had inner thigh pain (3.07%); seven had more severe pain that was improved by physical therapy.
Conclusion
PFNA-II has the advantages of a simple operation, few complications, and clinical efficacy for the treatment of intertrochanteric fractures. However, evaluation of its long-term efficacy and risk of other complications requires a large-sample, multicenter observational study.
doi:10.1186/s13018-014-0112-5
PMCID: PMC4233078  PMID: 25391985
20.  Functional expression, characterization and application of the human S100A4 protein 
Molecular Medicine Reports  2014;11(1):175-181.
Preparations utilizing monoclonal antibodies against S100A4 provide useful tools for functional studies to investigate the clinical applications of the human S100A4 protein. In the present study, human S100A4 protein was expressed in Escherichia coli (E. coli) BL21 (DE3), successfully purified by diethylaminoethyl cellulose anion-exchange chromatography and identified by western blot analysis. Soluble S100A4 bioactivity was confirmed by Transwell migration and invasion assays in the human HeLa cell line. Monoclonal antibodies (mAbs) were generated utilizing the standard hybridoma method and were validated by enzyme-linked immunosorbent assay and western blot analysis. The antibody was then used to examine human gastric carcinoma specimens by immunohistochemistry. Recombinant S100A4 was functionally expressed in E. coli and promoted the migration and invasion of HeLa cells. Four hybridoma cell lines, which secreted mAbs specifically against human S100A4 protein, were obtained. One of the four mAbs, namely 2A12D10B2, recognized human S100A4 as indicated by immunohistochemical staining of human gastric carcinoma specimens and recombinant S100A4 was functionally expressed in E. coli. The mAbs of recombinant S100A4 were suitable for detecting S100A4 expression in human tissues and for investigating the subsequent clinical applications of the protein.
doi:10.3892/mmr.2014.2745
PMCID: PMC4237081  PMID: 25339497
human S100A4 protein; monoclonal antibody; preparation; application
21.  The resistive switching memory of CoFe2O4 thin film using nanoporous alumina template 
Nanoscale Research Letters  2014;9(1):584.
A novel conductive process for resistive random access memory cells is investigated based on nanoporous anodized aluminum oxide template. Bipolar resistive switching characteristic is clearly observed in CoFe2O4 thin film. Stable and repeatable resistive switching behavior is acquired at the same time. On the basis of conductive filament model, possible generation mechanisms for the resistive switching behaviors are discussed intensively. Besides, the magnetic properties of samples (before and after the annealing process) are characterized, and the distinct changes of magnetic anisotropy and coercive field are detected. The present results provide a new perspective to comprehend the underlying physical origin of the resistive switching effect.
PACS
68.37.-d; 73.40.Rw; 73.61.-r
doi:10.1186/1556-276X-9-584
PMCID: PMC4232846  PMID: 25404869
Nanowire; Thin film; Electrochemical deposition; Resistive random access memory
22.  Fatal eosinophilic myocarditis develops in the absence of IFNγ and IL17A 
CD4+ T cells play a central role in inflammatory heart disease, implicating a cytokine product associated with helper T cell effector function as a necessary mediator of this pathophysiology. IFNγ-deficient mice developed severe autoimmune myocarditis (EAM), in which mice are immunized with cardiac myosin peptide, while IL17A-deficient mice were protected from progression to dilated cardiomyopathy. We generated IFNγ−/−IL17A−/− mice to assess whether IL17 signaling was responsible for the severe EAM of IFNγ−/− mice. Surprisingly, IFNγ−/−IL17A−/− mice developed a rapidly fatal EAM. Eosinophils comprised a third of infiltrating leukocytes, qualifying this disease eosinophilic myocarditis. We found increased cardiac production of CCL11/eotaxin, and Th2 deviation among heart-infiltrating CD4+ cells. Ablation of eosinophil development improved survival of IFNγ−/−IL17A−/− mice, demonstrating the necessity of eosinophils in fatal heart failure. The severe and rapidly fatal autoimmune inflammation that developed in the combined absence of IFNγ and IL17A constitutes a novel model of eosinophilic heart disease in humans. This is also the first demonstration that eosinophils have the capacity to act as necessary mediators of morbidity in an autoimmune process.
doi:10.4049/jimmunol.1301282
PMCID: PMC3927983  PMID: 24048893
myocarditis; autoimmune disease; cytokines; IFNγ; IL17A; eosinophils; Th2 cells
23.  BraLTP1, a Lipid Transfer Protein Gene Involved in Epicuticular Wax Deposition, Cell Proliferation and Flower Development in Brassica napus 
PLoS ONE  2014;9(10):e110272.
Plant non-specific lipid transfer proteins (nsLTPs) constitute large multigene families that possess complex physiological functions, many of which remain unclear. This study isolated and characterized the function of a lipid transfer protein gene, BraLTP1 from Brassica rapa, in the important oilseed crops Brassica napus. BraLTP1 encodes a predicted secretory protein, in the little known VI Class of nsLTP families. Overexpression of BnaLTP1 in B. napus caused abnormal green coloration and reduced wax deposition on leaves and detailed wax analysis revealed 17–80% reduction in various major wax components, which resulted in significant water-loss relative to wild type. BnaLTP1 overexpressing leaves exhibited morphological disfiguration and abaxially curled leaf edges, and leaf cross-sections revealed cell overproliferation that was correlated to increased cytokinin levels (tZ, tZR, iP, and iPR) in leaves and high expression of the cytokinin biosynthsis gene IPT3. BnaLTP1-overexpressing plants also displayed morphological disfiguration of flowers, with early-onset and elongated carpel development and outwardly curled stamen. This was consistent with altered expression of a a number of ABC model genes related to flower development. Together, these results suggest that BraLTP1 is a new nsLTP gene involved in wax production or deposition, with additional direct or indirect effects on cell division and flower development.
doi:10.1371/journal.pone.0110272
PMCID: PMC4196963  PMID: 25314222
24.  Panax ginseng therapy for chronic obstructive pulmonary disease: a clinical trial protocol and pilot study 
Chinese Medicine  2014;9:20.
Background
Panax ginseng (Ren shen) has been used to treat chronic obstructive pulmonary disease (COPD). This article aims to present a study protocol and pilot trial comparing P. ginseng with placebo for treating moderate to very severe COPD.
Methods
COPD was diagnosed spirometrically, with participants having a forced expiratory volume in one second (FEV1) of between 20% and 79% and FEV1 to forced vital capacity (FVC) ratio of less than 70%. Outcome measures included exacerbation rate, St. Georges Respiratory Questionnaire, COPD Assessment Test and Short-form Health Survey (SF-36). Other outcome measures included the six-minute walk test, FEV1, FVC, relief medication use, use of COPD-specific medical resources, and adverse events. The study is a randomized, double-blind, placebo controlled clinical trial. The method of this pilot trial was based on a planned full-scale trial except that participants were enrolled for ten weeks compared to 52 weeks. In the pilot trial, 14 participants (57–73 years old) with moderate to very severe COPD were recruited from a community health program at a public Chinese medicine hospital in Guangdong Province, China. After a 2-week run-in period, 10 participants were eligible for the study and were randomly assigned to either P. ginseng group (n = 5) (200 mg twice daily for four weeks) or placebo group (n = 5), and then followed-up for an additional 4 weeks for a total of 10 weeks.
Results
Nine participants completed the trial and one dropped out. The exacerbation rate could not be evaluated because there were no exacerbations. One participant in P. ginseng group reported events of sore throat, cough and fever. Trial investigators did not consider these events as COPD exacerbations or adverse events.
Conclusions
Participant recruitment, study design, data collection and outcome measurement have been tested in a pilot trial. A full-scale trial is warranted.
doi:10.1186/1749-8546-9-20
PMCID: PMC4144315  PMID: 25161696
25.  Association between Serum Uric Acid Level and Metabolic Syndrome and Its Sex Difference in a Chinese Community Elderly Population 
Objective. This study aimed to evaluate the association between serum uric acid (SUA) levels within a normal to high range and the risk of metabolic syndrome (MetS) among community elderly and explore the sex difference. Design and Methods. A cross-sectional study was conducted in a representative urban area of Beijing between 2009 and 2010. A two-stage stratified clustering sampling method was used and 2102 elderly participants were included. Results. The prevalence of hyperuricemia and MetS was 16.7% and 59.1%, respectively. There was a strong association between hyperuricemia and four components of MetS in women and three components in men. Multiple logistic regression analysis showed ORs of hyperuricemia for MetS were 1.67 (95% CI: 1.11–2.50) in men and 2.73 (95% CI: 1.81–4.11) in women. Even in the normal range, the ORs for MetS increased gradually according to SUA levels. MetS component number also showed an increasing trend across SUA quartile in both sexes (P for trend < 0.01). Conclusion. This study suggests that higher SUA levels, even in the normal range, are positively associated with MetS among Chinese community elderly, and the association is stronger in women than men. Physicians should recognize MetS as a frequent comorbidity of hyperuricemia and take early action to prevent subsequent disease burden.
doi:10.1155/2014/754678
PMCID: PMC4129973  PMID: 25136366

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