PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (99)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
more »
1.  Life events and chronic physical conditions among left-behind farmers in rural China a cross-sectional study 
BMC Public Health  2015;15:594.
Background
This study investigates the relationships between life events and chronic physical conditions among left behind farmers, a newly emerged weak group in vast rural China.
Methods
The study collected information about life events, chronic physical conditions, blood pressure and fasting blood glucose from 4681 famers living in 18 randomly selected villages (Lu’an, Anhui, China) from early November 2013 to the end of December 2013. It compared the risk and odds ratios (RRs/ORs) among different subgroups divided according two life event indices derived by adding up un-weighted-ratings and weighted-ratings based on multivariate logistic regression coefficients respectively.
Results
A total of 4040 (86.3 % eligible) farmers completed the survey. RRs between farmers with lower than the first 1/15-percentile of life event index and with higher life event index scores ranged 1.43–5.79 for chronic gastritis and 0.42–9.07 for prostatitis, 1.01–4.97 for cervicitis/vaginitis, 1.45–3.28 for cardio-cerebrovascular diseases, 1.12–1.58 for hypertension, 1.00–1.66 for diabetes, 1.07–3.35 for pre-diabetes and 5.00–55.00 for “other chronic physical conditions”.
Conclusions
Life events were independently linked with most of the chronic physical conditions in a dose-effectiveness way. RRs between subgroups divided by given percentile cutoff points of life event index compiled using logistic regression models turned out to be substantially higher than that between subgroups divided by same cutoff points of life event index produced via summing up the un-weighted Likert ratings of all the events studied.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-015-1877-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12889-015-1877-0
PMCID: PMC4487061  PMID: 26130045
Life events; Chronic diseases; Risk ratio; Odds ratio; Index; Logistic regression
2.  Tutorial in Biostatistics: Instrumental Variable Methods for Causal Inference* 
Statistics in medicine  2014;33(13):2297-2340.
A goal of many health studies is to determine the causal effect of a treatment or intervention on health outcomes. Often, it is not ethically or practically possible to conduct a perfectly randomized experiment and instead an observational study must be used. A major challenge to the validity of observational studies is the possibility of unmeasured confounding (i.e., unmeasured ways in which the treatment and control groups differ before treatment administration which also affect the outcome). Instrumental variables analysis is a method for controlling for unmeasured confounding. This type of analysis requires the measurement of a valid instrumental variable, which is a variable that (i) is independent of the unmeasured confounding; (ii) affects the treatment; and (iii) affects the outcome only indirectly through its effect on the treatment. This tutorial discusses the types of causal effects that can be estimated by instrumental variables analysis; the assumptions needed for instrumental variables analysis to provide valid estimates of causal effects and sensitivity analysis for those assumptions; methods of estimation of causal effects using instrumental variables; and sources of instrumental variables in health studies.
doi:10.1002/sim.6128
PMCID: PMC4201653  PMID: 24599889
instrumental variables; observational study; confounding; comparative effectiveness
3.  Chemical synthesis of a two-photon-activatable chemokine and photon-guided lymphocyte migration in vivo 
Nature Communications  2015;6:7220.
Chemokine-guided lymphocyte positioning in tissues is crucial for normal operation of the immune system. Direct, real-time manipulation and measurement of single-cell responses to chemokines is highly desired for investigating the cell biology of lymphocyte migration in vivo. Here we report the development of the first two-photon-activatable chemokine CCL5 through efficient one-pot total chemical synthesis in milligram scale. By spatiotemporally controlled photoactivation, we show at the single-cell level that T cells perceive the directional cue without relying on PI3K activities, which are nonetheless required for persistent migration over an extended period of time. By intravital imaging, we demonstrate artificial T-cell positioning in cutaneous tissues and lymph nodes. This work establishes a general strategy to develop high-quality photo-activatable protein agents through tailor-designed caging of multiple residues and highlights the potential of photo-activatable chemokines for understanding and potential therapeutic manipulation of cell positioning and position-controlled cell behaviours in vivo.
The precise spatiotemporal control of chemokine exposure would be an advantageous tool for immune cell research. Here, Chen et al. develop a two-photon-activatable chemokine CCL5 and use it to direct lymphocyte migration in vivo and to show that PI3-kinase is not required to sense a gradient in vitro.
doi:10.1038/ncomms8220
PMCID: PMC4455097  PMID: 26008852
4.  Phosphorylation of Carma1, but not Bcl10, by Akt regulates TCR/CD28-mediated NF-κB induction and cytokine production 
Molecular immunology  2014;59(1):110-116.
Previous studies from our group and others have shown that the Akt kinase can contribute to induction of NF-κB by antigen receptor signaling. However, the direct targets of Akt in this pathway are not known. Here we show that Akt-mediated NF-κB activation is mediated at least in part through direct phosphorylation of the adaptor protein Carma1, which we previously demonstrated could interact with Akt in a TCR ligation-dependent manner. The putative Akt phosphorylation sites in Carma1 are distinct from known PKC consensus sites. Mutation of S551, S637 and S645 in Carma1 to non-phosphorylatable residues decreased phosphorylation of GST-Carma1-linker construct by Akt in vitro. In addition, Carma1 S637A/S645A mutants were significantly impaired in their ability to restore TCR-mediated NF-κB activation and IL-2 expression in Carma1-deficient T cells. Thus, our data reveal Carma1 as a novel target for Akt phosphorylation and suggest that Akt-mediated phosphorylation of Carma1 is an additional regulatory mechanism tuning the NF-κB response downstream of antigen receptor and co-stimulatory signaling.
doi:10.1016/j.molimm.2014.01.011
PMCID: PMC3968090  PMID: 24548923
Signal transduction; NF-κB; T cells; Phosphorylation; Akt
5.  A missense mutation in TMEM67 causes Meckel-Gruber syndrome type 3 (MKS3): a family from China 
Meckel-Gruber syndrome (MKS) is a lethal autosomal recessive condition characterized by renal cysts and variably associated features, including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. Genetic heterogeneity has been demonstrated at eleven loci, MKS1-11. Here, we present the clinical and molecular characteristics of a Chinese MKS3 family with occipital encephalocele and kidney enlargement. DNA sequencing of affected fetuses revealed a homozygous c.1645C>T substitution in exon 16 of TMEM67, leading to a p.R549C substitution in meckelin. The R549 residue is highly conserved across human, rat, mouse, zebrafish, chicken, wolf and platypus genomes. Hha I restriction analysis demonstrated that the c.1645C>T mutation was absent in 200 unrelated control chromosomes of Chinese background, supporting the hypothesis that it represents causative mutation, not rare polymorphism. Our data provide additional molecular and clinical information for establishing a better genotype-phenotype understanding of MKS.
PMCID: PMC4503111  PMID: 26191240
MKS3; TMEM67; meckelin; mutation
6.  A Carma1/MALT1-dependent, Bcl10-independent, pathway regulates antigen receptor-mediated mTOR signaling in T cells 
Science signaling  2014;7(329):ra55.
Signaling to the mechanistic target of rapamycin (mTOR) regulates diverse cellular processes, including protein translation, cellular proliferation, metabolism, and autophagy. These effects are mediated in part by the mTOR targets S6 kinase (S6K) and eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). Most models place Akt upstream of the best-studied mTOR complex, mTORC1; however, studies have called into question whether Akt is necessary for this pathway, at least in T cells. We found that the adaptor protein Carma1 [caspase recruitment domain (CARD)-containing membrane-associated protein 1 (Carma1)] and at least one of its associated proteins, the paracaspase MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), were required for optimal activation of mTOR in T cells in response to stimulation of the T cell receptor (TCR) and the coreceptor CD28. However, another common binding partner of Carma1 and MALT1, Bcl10, was not required for TCR-dependent activation of the mTOR pathway. Consistent with these findings, MALT1 activity was required for the proliferation of CD4+ T cells, but not early TCR-dependent activation events. Also consistent with an effect on mTOR, MALT1 activity was required for the increased metabolic flux in activated CD4+ T cells. Together, our data suggest that Carma1 and MALT1 play previously unappreciated roles in the activation of mTOR signaling in T cells after engagement of the TCR.
doi:10.1126/scisignal.2005169
PMCID: PMC4405131  PMID: 24917592
7.  eCROPS-CA: a systematic approach toward effective and sustainable cancer prevention in rural China 
BMC Cancer  2015;15:233.
Background
Effective prevention against cancers depends heavily on sustained individual efforts practicing protective behaviors and avoiding risk factors in a complex sociocultural context, which requires continuous and personalized supports. Contemporary prevention relies primarily on strategies targeting general population with limited attention being paid to individualized approaches. This study tests a novel package called, in acronym of core intervention components, eCROPS-CA that leverages protective behaviors against over 80% leading cancers among high risk individuals via continuous and tailored counseling by village doctors.
Methods/Design
The study utilizes a quesi-RCT design involving 4320 high risk individuals selected, via rapid and detailed risk assessments, from about 72,000 farmers aged 35+ in 36 administrative villages randomized into equal intervention and delayed intervention arms. The intervention arm receives baseline and semiannual follow up evaluations plus eCROPS-CA for 5 years; while the control arm, only the baseline and follow-up evaluations for the first 5 years and eCROPS-CA starting from the 6th year if the intervention is proved effective. eCROPS-CA comprises electronic supports and supervision (e), counseling cancer prevention (C), recipe for objective behaviors (R), operational toolkit (O), performance-based incentives (P), and screening and assessment (S). Evaluation measures include: incidence and stage of the leading cancers, cancer-related knowledge, attitudes and practices; easy biophysical indicators (e.g., body mass index, blood pressure); intervention compliance, acceptance of the package.
Discussion
The prevention package incorporates key success factors in a synergetic way toward cost-effectiveness and long-term sustainability. It targets a set rather than any single cancer; choses village doctors as key solution to the widespread lack of professional manpower in implementing personalized and thus relatively sophisticated prevention; adopts real-time monitoring in reaching continuous improvement; utilizes smart web aids to enable prioritizing complex determinants of objective behaviors, linking counseling sessions happened at different time points and hence delivering highly coordinated prevention; uses 2-stage risk assessment models in identifying high risk individuals so as to focus on the most needed; applies standardized operation procedures in simplifying and smoothing behavior intervention yet ensuring delivery of essential steps and key elements.
Trials registry
ISRCTN33269053
Electronic supplementary material
The online version of this article (doi:10.1186/s12885-015-1253-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s12885-015-1253-6
PMCID: PMC4416351  PMID: 25886568
Cancer; Behavior intervention; Rural communities; Randomized controlled trail; Service integration
8.  Accumulation of p53 is prognostic for aromatase inhibitor resistance in early-stage postmenopausal patients with ER-positive breast cancer 
OncoTargets and therapy  2015;8:549-555.
Objective
Studies have indicated that p53 protein accumulation exerts an adverse effect on the survival of breast cancer patients; however, the prognostic value of p53 protein accumulation for aromatase inhibitor (AI) resistance in ER-positive breast cancer is uncertain.
Methods
The expression level of p53 protein was detected by immunohistochemistry in primary early-stage ER-positive breast tumor specimens from 293 postmenopausal breast cancer patients who received first-line AI treatment (letrozole, anastrozole, or exemestane) until relapse, and analysis was performed to determine whether expression of p53 protein affected the response to endocrine therapy.
Results
Of the 293 invasive ductal carcinomas, 65.4% were positive for p53 protein expression. All patients received AI therapy as first-line treatment until relapse. The 5-year disease-free survival rates in p53-positive and p53-negative patients were 78% and 89%, respectively. Patients with primary breast tumors that had p53 protein accumulation showed significantly more resistance to AI treatment (hazard ratio=1.729, 95% confidence interval=1.038–2.880, P=0.035).
Conclusion
This study demonstrated that p53 protein accumulation was helpful in choosing patients who may benefit from AI treatment and is a prognostic marker in ER-positive early-stage breast cancer.
doi:10.2147/OTT.S76879
PMCID: PMC4354449  PMID: 25767399
p53; breast cancer; prognosis; endocrine resistance
9.  Genetic predisposition of stroke: understanding the evolving landscape through meta-analysis 
Stroke, either ischemic or hemorrhagic, is the leading cause of death and morbidity worldwide. Identifying the risk factors is a prerequisite step for stroke prevention and treatment. It is believed that a major portion of the currently unidentified risk factors is of genetic origin. Consistent with this idea, numerous potential risk alleles for stroke have been reported, however, the genetic evidence so far is not conclusive. The major goal of this review is to update the current knowledge about the genetic predisposition to the common multifactorial stroke, and to provide a bird’s-eye view of this fast moving field. We selectively review and meta-analyze the related English literatures in public domain (PubMed) from 2000 onward, including the original reports and meta-analyses, to evaluate the genetic risk factors of common multifactorial stroke. The results indicated that we reviewed and meta-analyzed original reports and existing meta-analyses that studied the genetic predisposition to the common multifactorial stroke. Some original reports and meta-analyses were specific for ischemic stroke and others were for hemorrhagic stroke only. We also evaluated the major evolving issues in this field and discussed the future directions. In conclusion, strong evidences suggest that genetic risk factors contribute to common multifactorial stroke, and many genetic risk genes have been implicated in the literatures. However, not a single risk allele has been conclusively approved.
PMCID: PMC4358587  PMID: 25785132
Genetic predisposition/risk; ischemic stroke; hemorrhagic stroke
10.  Predictive value of vascular endothelial growth factor polymorphisms on the clinical outcome of renal cell carcinoma patients 
Oncology Letters  2014;9(2):651-656.
A cohort study was conducted to investigate the association between vascular endothelial growth factor (VEGF) polymorphisms −2578C/A, −1154G/A and −634C/G and the clinical outcome of renal cell carcinoma (RCC), as well as the interaction of VEGF polymorphisms with tumor stage, metastasis and size. A total of 310 RCC patients were recruited from the First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between January 2006 and December 2007, and were followed up until December 2012. The association between the three single nucleotide polymorphisms and the overall survival of RCC patients was estimated using Cox’s proportional hazard regression model. The median follow-up duration was 34.7 months and 74 of the RCC patients succumbed due to cancer during the follow-up period. The frequency of the VEGF −2578 AA genotype was significantly higher in patients classed as tumor stages III–IV (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.24–0.95) and larger tumors (longest diameter, >4 cm; OR, 0.44; 95% CI, 0.22–0.89). Furthermore, the frequency of VEGF −634 GG was significantly higher in patients with larger tumors (longest diameter, >4 cm; OR, 0.68; 95% CI, 0.48–0.97). The VEGF −2578 AA genotype was correlated with a 2.96-fold increase in the risk of RCC-associated mortality and was associated with a five-year survival rate of ~25%. Therefore, the present study identified that the VEGF −2578C/A polymorphism may be associated with the prognosis of RCC patients, and may interact with the tumor stage and size.
doi:10.3892/ol.2014.2798
PMCID: PMC4301497  PMID: 25621033
renal cell carcinomas; vascular endothelial growth factor; clinical outcome; polymorphism
11.  Identification of Differentially-expressed Genes in Intestinal Gastric Cancer by Microarray Analysis 
Gastric cancer (GC) is one of the most frequent malignant tumors. In order to systematically characterize the cellular and molecular mechanisms of intestinal GC development, in this study, we used 22 K oligonucleotide microarrays and bioinformatics analysis to evaluate the gene expression profiles of GC in 45 tissue samples, including 20 intestinal GC tissue samples, 20 normal appearing tissues (NATs) adjacent to tumors and 5 noncancerous gastric mucosa tissue samples. These profiles allowed us to explore the transcriptional characteristics of GC and determine the change patterns in gene expression that may be of clinical significance. 1519 and 1255 differentially-expressed genes (DEGs) were identified in intestinal GC tissues and NATs, respectively, as determined by Bayesian analysis (P < 0.001). These genes were associated with diverse functions such as mucosa secretion, metabolism, proliferation, signaling and development, which occur at different stages of GC development.
doi:10.1016/j.gpb.2014.09.004
PMCID: PMC4411479  PMID: 25500430
Gastric cancer development; Microarray; Gene expression profile
12.  Oral Health Education for Pediatric Nurse Practitioner Students 
Journal of dental education  2013;77(5):581-590.
The aim of this study was to evaluate whether an interdisciplinary, multifaceted oral health education program delivered to pediatric nurse practitioner students at the University of California, San Francisco, would improve their knowledge, confidence, attitudes, and behaviors regarding the provision of oral health assessments, consultations, referrals, and services to young children during well-child visits. Thirty pediatric nurse practitioner students were included in the study. Participants completed a written survey before and after receiving an interdisciplinary educational intervention that included didactic education, simulation exercises, and clinical observation by a pediatric dental resident. Between pre-intervention and post-intervention, a significant improvement was seen in the pediatric nurse practitioners’ knowledge of oral health topics (p<0.001), confidence when providing oral health counseling (p<0.001), and attitudes about including oral health counseling in their examinations (p=0.006). In the post-intervention survey, 83 percent of the subjects reported having incorporated oral examinations into their well-child visits. Our study suggests that providing an interdisciplinary oral health educational program for pediatric nurse practitioner students can improve their knowledge, confidence, attitudes, and behaviors regarding the incorporation of oral health care services during routine well-child visits.
PMCID: PMC4259151  PMID: 23658403
oral health education; pediatric nurse practitioner students; interdisciplinary education; interprofessional education; well-child visits
13.  KCNJ10 May Not Be a Contributor to Nonsyndromic Enlargement of Vestibular Aqueduct (NSEVA) in Chinese Subjects 
PLoS ONE  2014;9(11):e108134.
Background
Nonsyndromic enlargement of vestibular aqueduct (NSEVA) is an autosomal recessive hearing loss disorder that is associated with mutations in SLC26A4. However, not all patients with NSEVA carry biallelic mutations in SLC26A4. A recent study proposed that single mutations in both SLC26A4 and KCNJ10 lead to digenic NSEVA. We examined whether KCNJ10 excert a role in the pathogenesis of NSEVA in Chinese patients.
Methods
SLC26A4 was sequenced in 1056 Chinese patients with NSEVA. KCNJ10 was screened in 131 patients who lacked mutations in either one or both alleles of SLC26A4. Additionally, KCNJ10 was screened in 840 controls, including 563 patients diagnosed with NSEVA who carried biallelic SLC26A4 mutations, 48 patients with nonsyndromic hearing loss due to inner ear malformations that did not involve enlargement of the vestibular aqueduct (EVA), 96 patients with conductive hearing loss due to various causes, and 133 normal-hearing individuals with no family history of hereditary hearing loss.
Results
925 NSEVA patients were found carrying two-allele pathogenic SLC26A4 mutations. The most frequently detected KCNJ10 mutation was c.812G>A (p.R271H). Compared with the normal-hearing control subjects, the occurrence rate of c.812G>A in NSEVA patients with lacking mutations in one or both alleles of SLC26A4 had no significant difference(1.53% vs. 5.30%, χ2 = 2.798, p = 0.172), which suggested that it is probably a nonpathogenic benign variant. KCNJ10 c.1042C>T (p.R348C), the reported EVA-related mutation, was not found in patients with NSEVA who lacked mutations in either one or both alleles of SLC26A4. Furthermore, the normal-hearing parents of patients with NSEVA having two SLC26A4 mutations carried the KCNJ10 c.1042C>T or c.812G>A mutation and a SLC26A4 pathogenic mutation.
Conclusion
SLC26A4 is the major genetic cause in Chinese NSEVA patients, accounting for 87.59%. KCNJ10 may not be a contributor to NSEVA in Chinese population. Other genetic or environmental factors are possibly play a role in the etiology of Chinese EVA patients with zero or monoallelic SLC26A4 mutation.
doi:10.1371/journal.pone.0108134
PMCID: PMC4220913  PMID: 25372295
14.  Systematic profiling of mRNA and miRNA expression in the pancreatic islets of spontaneously diabetic Goto-Kakizaki rats 
Molecular Medicine Reports  2014;11(1):67-74.
Type 2 diabetes (T2DM) is a complex multifactorial metabolic disorder that affects >100 million individuals worldwide, yet the mechanisms involved in the development and progression of the disease have not yet been fully elucidated. The present study examined the mRNA and micro (mi)RNA expression profiles by microarray analysis in the pancreas islets of spontaneously diabetic Goto-Kakizaki rats with the aim to identify regulatory mechanisms underlying the pathogenesis of T2DM. A total of 9 upregulated and 10 downregulated miRNAs were identified, including miR-150, miR-497, miR-344-3p and let-7f, which were independently validated by quantitative polymerase chain reaction assays. In addition, differential expression of 670 genes was detected by mRNA microarray analysis, including 370 upregulated and 247 downregulated genes. The differentially expressed genes were statistically associated with major cellular pathways, including the immune response pathway and the extracellular matrix (ECM)-receptor interaction pathway. Finally, a reverse regulatory association of differentially expressed miRNAs and their predicted target genes was constructed, supported by analysis of their mRNA and miRNA expression profiles. A number of key pairs of miRNA-mRNA was proposed to have significant roles in the pathogenesis of T2DM rats based on bioinformatics analysis, one example being the let-7f/collagen, type II, alpha 1 pair that may regulate ECM-receptor interactions.
doi:10.3892/mmr.2014.2723
PMCID: PMC4237099  PMID: 25333294
type 2 diabetes; gene expression array; microRNA microarray; microRNA-mRNA regulatory correlation
15.  Effects of zedoary turmeric oil on P450 activities in rats with liver cirrhosis induced by thioacetamide 
The aim of this study was to elucidate the effects of zedoary turmeric oil (ZTO) on P450 activities (CYP1A2, CYP2C9, CYP2C19, CYP2B6, CYP2D6 and CYP3A4) in rats with liver cirrhosis induced by thioacetamide (TAA). For the induction of liver cirrhosis, rats were given TAA in their drinking water at a concentration of 0.03% for consecutive 5 weeks and then 0.04% for the next consecutive 5 weeks throughout the establishment of cirrhosis. Then the cirrhotic rats were ip given saline, ZTO 100, 200 and 400 mg/kg, respectively, once daily for 2 weeks. When cirrhosis model was established at week 10, all rats of five groups were administered intragastrically with 15 mg/kg phenacetin, 0.6 mg/kg tolbutamide, 15 mg/kg omeprazole, 15 mg/kg bupropion, 15 mg/kg metoprolol, and 10 mg/kg midazolam. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The degree of liver cirrhosis was assessed by HE staining. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from the model group increased by approximately 4-fold, and a decreased level of albumin (Alb) was also observed, as compared to the control group (P < 0.05). However, ZTO was found to reverse those changes of serum levels observed in the model group, and the 200 mg/kg ZTO treatment group showed the most obvious reverse tendency with significantly decreased ALT, AST and increased Alb levels (P < 0.05). The results indicated that ZTO with the dose of 100 mg/kg could inhibit the activities of CYP450 isoforms CYP2C9 and CYP2D6 in vivo in cirrhotic rats induced by TAA, while ZTO with the dose of 400 mg/kg could induce the activity of CYP2C19 in vivo in cirrhotic rats induced by TAA. However, ZTO showed no influence on cirrhotic rat hepatic CYP1A2, CYP2B6 and CYP3A4 activity in vivo. This has certain guiding significance to clinical treatment.
PMCID: PMC4270516  PMID: 25550825
Zedoary turmeric oil; CYP450; liver cirrhosis; rat; thioacetamide
16.  Diet Type and Changes in Food Cravings following Weight Loss: Findings from the POUNDS LOST Trial 
Eating and weight disorders : EWD  2012;17(2):e101-e108.
Few well-controlled trials have evaluated the effects that macronutrient composition has on changes in food cravings during weight loss treatment. The present study, which was part of the POUNDS LOST trial, investigated whether the fat and protein content of four different diets affected changes in specific food cravings in overweight and obese adults. A sample of 811 adults were recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: (1) Low fat (20% of energy), average protein (15% of energy); (2) Moderate fat (40%), average protein (15%); (3) Low fat (20%), high protein (25%); (4) Moderate fat (40%), high protein (25%). With few exceptions, the type of diet that participants were assigned did not differentially affect changes in specific food cravings. Participants assigned to the high fat diets, however, had reduced cravings for carbohydrates at Month12 (p< .05) and fruits and vegetables at Month 24. Also, participants assigned to high protein diets had increased cravings for sweets at Month 6 (p< .05). Participants in all four dietary conditions reported significant reductions in food cravings for specific types of foods (i.e., high fat foods, fast food fats, sweets, and carbohydrates/starches; all ps< .05). Cravings for fruits and vegetables, however, were increased at Month 24 (p< .05). Calorically restricted diets (regardless of their macronutrient composition) yielded significant reductions in cravings for fats, sweets, and starches whereas cravings for fruits and vegetables were increased.
PMCID: PMC4189179  PMID: 23010779
Macronutrient composition; Caloric restriction; Food type; Fat; Carbohydrate; Protein
17.  An Efficient Genotyping Method for Genome-modified Animals and Human Cells Generated with CRISPR/Cas9 System 
Scientific Reports  2014;4:6420.
The rapid generation of various species and strains of laboratory animals using CRISPR/Cas9 technology has dramatically accelerated the interrogation of gene function in vivo. So far, the dominant approach for genotyping of genome-modified animals has been the T7E1 endonuclease cleavage assay. Here, we present a polyacrylamide gel electrophoresis-based (PAGE) method to genotype mice harboring different types of indel mutations. We developed 6 strains of genome-modified mice using CRISPR/Cas9 system, and utilized this approach to genotype mice from F0 to F2 generation, which included single and multiplexed genome-modified mice. We also determined the maximal detection sensitivity for detecting mosaic DNA using PAGE-based assay as 0.5%. We further applied PAGE-based genotyping approach to detect CRISPR/Cas9-mediated on- and off-target effect in human 293T and induced pluripotent stem cells (iPSCs). Thus, PAGE-based genotyping approach meets the rapidly increasing demand for genotyping of the fast-growing number of genome-modified animals and human cell lines created using CRISPR/Cas9 system or other nuclease systems such as TALEN or ZFN.
doi:10.1038/srep06420
PMCID: PMC4168274  PMID: 25236476
18.  Urinary interleukin-18 as an early indicator to predict contrast-induced nephropathy in patients undergoing percutaneous coronary intervention 
Contrast-induced nephropathy (CIN) is at present the third leading cause of hospital-acquired acute kidney injury (AKI). Traditionally, it is diagnosed by measuring an increase of the serum creatinine (SCr) concentration. However, SCr is an insensitive marker for detecting CIN. This study was designed to investigate whether human urinary interleukin-18 (IL-18) is early predictive marker for CIN following coronary interventional procedures. The general clinical data of 180 patients who underwent coronary interventional procedures at the Department of Cardiology, Affiliated Hospital of Xuzhou Medical College from March 1, 2012 to September 31, 2012 were collected. A nonionic, low osmolality contrast agent was used in the laboratory at this time. SCr values and estimated glomerular filtration rate (eGFR) were measured prior to and within 24 and 48 h after the administration of contrast agents. Urine samples were collected prior to and 2, 6, 12, 24 and 48 h after the coronary interventional procedure, and urinary IL-18 levels were measured using an ELISA kit. CIN was defined as an increase of ≥0.5 mg/dl or ≥25% in SCr concentration over baseline 24–48 h after the procedure. CIN occurred in 16 of 180 (8.9%) patients. The levels of urinary IL-18 measured 2 h after the procedure were increased in the CIN group, but the increase was not significant (P>0.05). There were significant differences (P<0.05) between the urinary IL-18 levels 6, 12, 24 and 48 h after the procedure and those before the procedure. No significant difference was identified between the SCr levels measured prior to and 24 h after the procedure. The area under the receiver operating characteristic (ROC) curve of urinary IL-18 12 h after the procedure was 0.811 and the 95% confidence interval of the area under the curve was 0.735–0.888. If the critical point of the diagnosis of CIN was 815.61 pg/ml, the sensitivity was 87.5% and the specificity was 62.2%. Univariate analysis indicated that the urinary IL-18 level was positively correlated with the SCr concentration pre- and postprocedure. In conclusion, urinary IL-18 may be a promising indicator for the early prediction of CIN.
doi:10.3892/etm.2014.1898
PMCID: PMC4151647  PMID: 25187836
interleukin-18; coronary artery angiography; contrast-induced nephropathy
19.  Regulation of NF-κB induction by TCR/CD28 
Immunologic research  2011;50(0):113-117.
NF-κB family transcription factors are a common downstream target for inducible transcription mediated by many different cell-surface receptors, especially those receptors involved in inflammation and adaptive immunity. It is now clear that different classes of receptors employ different proximal signaling strategies to activate the common NF-jB signaling components, such as the IKK complex. For antigen receptors expressed by T and B cells, this pathway requires a complex of proteins including the proteins Carma1, Bcl10, and Malt1. Here, we discuss some of what is known about regulation of these proteins downstream of TCR/CD3 and co-stimulatory CD28 signaling. We also discuss another unique aspect of TCR-mediated NF-κB activation, i.e., the spatial restriction imposed on signaling events by the formation of the immunological synapse between a T cell and antigen-presenting cell presenting specific peptide/MHC.
doi:10.1007/s12026-011-8216-z
PMCID: PMC4066383  PMID: 21717079
T cells; NF-κB; Signal transduction
20.  Decreased LINE-1 methylation levels in aldosterone-producing adenoma 
Purpose: Abnormal global DNA methylation levels are associated with many diseases. In this study, we examined long interspersed nuclear elements-1 (LINE-1) methylation as a biomarker for abnormal global DNA methylation and aldosterone-producing adenoma (APA). Methods: Tissues from 25 APA and 6 normal adrenal glands (NAs) were analyzed for LINE-1 methylation by real-time methylation-specific polymerase chain reaction. The estimated LINE-1 methylation level was then tested for correlation with the clinicopathologic parameters of APA patients. Results: The methylation index (MI) level for LINE-1 was 0.91 in NA samples and 0.77 in APA samples (P < 0.001). For the APA samples, there were no statistical correlations between the MI level and various clinicopathologic parameters such as gender (P = 0.07). Conclusion : LINE-1 methylation is significantly lower in APA samples than in NA samples. LINE-1 methylation is not correlated with the clinical characteristics of APA.
PMCID: PMC4129024  PMID: 25120789
Long interspersed nuclear elements-1; global DNA methylation; aldosterone-producing adenoma
21.  The ARL2 GTPase Is Required for Mitochondrial Morphology, Motility, and Maintenance of ATP Levels 
PLoS ONE  2014;9(6):e99270.
ARF-like 2 (ARL2) is a member of the ARF family and RAS superfamily of regulatory GTPases, predicted to be present in the last eukaryotic common ancestor, and essential in a number of model genetic systems. Though best studied as a regulator of tubulin folding, we previously demonstrated that ARL2 partially localizes to mitochondria. Here, we show that ARL2 is essential to a number of mitochondrial functions, including mitochondrial morphology, motility, and maintenance of ATP levels. We compare phenotypes resulting from ARL2 depletion and expression of dominant negative mutants and use these to demonstrate that the mitochondrial roles of ARL2 are distinct from its roles in tubulin folding. Testing of current models for ARL2 actions at mitochondria failed to support them. Rather, we found that knockdown of the ARL2 GTPase activating protein (GAP) ELMOD2 phenocopies two of three phenotypes of ARL2 siRNA, making it a likely effector for these actions. These results add new layers of complexity to ARL2 signaling, highlighting the need to deconvolve these different cell functions. We hypothesize that ARL2 plays essential roles inside mitochondria along with other cellular functions, at least in part to provide coupling of regulation between these essential cell processes.
doi:10.1371/journal.pone.0099270
PMCID: PMC4050054  PMID: 24911211
22.  A Smart Web Aid for Preventing Diabetes in Rural China: Preliminary Findings and Lessons 
Background
Increasing cases of diabetes, a general lack of routinely operational prevention, and a long history of separating disease prevention and treatment call for immediate engagement of frontier clinicians. This applies especially to village doctors who work in rural China where the majority of the nation’s vast population lives.
Objective
This study aims to develop and test an online Smart Web Aid for Preventing Type 2 Diabetes (SWAP-DM2) capable of addressing major barriers to applying proven interventions and integrating diabetes prevention into routine medical care.
Methods
Development of SWAP-DM2 used evolutionary prototyping. The design of the initial system was followed by refinement cycles featuring dynamic interaction between development of practical and effective standardized operation procedures (SOPs) for diabetes prevention and Web-based assistance for implementing the SOPs. The resulting SOPs incorporated proven diabetes prevention practices in a synergetic way. SWAP-DM2 provided support to village doctors ranging from simple educational webpages and record maintenance to relatively sophisticated risk scoring and personalized counseling. Evaluation of SWAP-DM2 used data collected at baseline and 6-month follow-up assessment: (1) audio recordings of service encounters; (2) structured exit surveys of patients’ knowledge, self-efficacy, and satisfaction; (3) measurement of fasting glucose, body mass index, and blood pressure; and (4) qualitative interviews with doctors and patients. Data analysis included (1) descriptive statistics of patients who received SWAP-DM2–assisted prevention and those newly diagnosed with prediabetes and diabetes; (2) comparison of the variables assessed between baseline and follow-up assessment; and (3) narratives of qualitative data.
Results
The 17 participating village doctors identified 2219 patients with elevated diabetes risk. Of these, 84.85% (1885/2219) consented to a fasting glucose test with 1022 new prediabetes and 113 new diabetes diagnoses made within 6 months. The prediabetic patients showed substantial improvement from baseline to 6-month follow-up in vegetable intake (17.0%, 43/253 vs 88.7%, 205/231), calorie intake (1.6%, 4/253 vs 71.4%, 165/231), leisure-time exercises (6.3%, 16/253 vs 21.2%, 49/231), body weight (mean 62.12 kg, SD 9.85 vs mean 58.33 kg, SD 9.18), and body mass index (mean 24.80 kg/m2, SD 3.21 vs mean 23.36 kg/m2, SD 2.95). The prediabetic patients showed improvement in self-efficacy for modifying diet (mean 5.31, SD 2.81 vs mean 8.53, SD 2.25), increasing physical activities (mean 4.52, SD 3.35 vs mean 8.06, SD 2.38), engaging relatives (mean 3.93, SD 3.54 vs mean 6.93, SD 2.67), and knowledge about diabetes and risks of an imbalanced diet and inadequate physical activity. Most participating doctors and patients viewed SWAP-DM2 as useful and effective.
Conclusions
SWAP-DM2 is helpful to village doctors, acceptable to patients, and effective in modifying immediate determinants of diabetes at least in the short term, and may provide a useful solution to the general lack of participation in diabetes prevention by frontier clinicians in rural China.
Trial Registration
International Standard Randomized Controlled Trial Number (ISRCTN): 66772711; http://www.controlled-trials.com/ISRCTN66772711 (Archived by WebCite at http://www.webcitation.org/6OMkAqyEy).
doi:10.2196/jmir.3228
PMCID: PMC4004141  PMID: 24691410
diabetes mellitus; prediabetic state; Internet; prevention; evaluation; eHealth
23.  Selective Inhibition of PI3K/Akt/mTOR Signaling Pathway Regulates Autophagy of Macrophage and Vulnerability of Atherosclerotic Plaque 
PLoS ONE  2014;9(3):e90563.
Macrophage infiltration contributes to the instability of atherosclerotic plaques. In the present study, we investigated whether selective inhibition of PI3K/Akt/mTOR signaling pathway can enhance the stability of atherosclerotic plaques by activation of macrophage autophagy. In vitro study, selective inhibitors or siRNA of PI3K/Akt/mTOR pathways were used to treat the rabbit's peritoneal primary macrophage cells. Inflammation related cytokines secreted by macrophages were measured. Ultrastructure changes of macrophages were examined by transmission electron microscope. mRNA or protein expression levels of autophagy related gene Beclin 1, protein 1 light chain 3 II dots (LC3-II) or Atg5-Atg12 conjugation were assayed by quantitative RT-PCR or Western blot. In vivo study, vulnerable plaque models were established in 40 New Zealand White rabbits and then drugs or siRNA were given for 8 weeks to inhibit the PI3K/Akt/mTOR signaling pathway. Intravascular ultrasound (IVUS) was performed to observe the plaque imaging. The ultrastructure of the abdominal aortic atherosclerosis lesions were analyzed with histopathology. RT-PCR or Western blot methods were used to measure the expression levels of corresponding autophagy related molecules. We found that macrophage autophagy was induced in the presence of Akt inhibitor, mTOR inhibitor and mTOR-siRNA in vitro study, while PI3K inhibitor had the opposite role. In vivo study, we found that macrophage autophagy increased significantly and the rabbits had lower plaque rupture incidence, lower plaque burden and decreased vulnerability index in the inhibitors or siRNA treated groups. We made a conclusion that selective inhibition of the Akt/mTOR signal pathway can reduce macrophages and stabilize the vulnerable atherosclerotic plaques by promoting macrophage autophagy.
doi:10.1371/journal.pone.0090563
PMCID: PMC3944201  PMID: 24599185
24.  Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease 
Nature genetics  2012;44(8):890-894.
We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases with coronary artery disease and 5,019 controls, followed by de novo replication studies in 15,460 cases and 11,472 controls, all of Chinese Han descent. We successfully identified four new loci for coronary artery disease reaching genome-wide significance (P < 5 × 10−8), which mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (PHACTR1, TCF21, CDKN2A/B and C12orf51). These findings provide new insights into biological pathways for the susceptibility of coronary artery disease in Chinese Han population.
doi:10.1038/ng.2337
PMCID: PMC3927410  PMID: 22751097
25.  A new mutation in the CSB gene in a Chinese patient with mild Cockayne syndrome 
Clinical Case Reports  2014;2(2):33-36.
Key Clinical Message
Cockayne syndrome (CS) is a rare autosomal recessive genetic disease characterized by growth failure and progressive neurological degeneration. Here we report a mild form of CS patient who was homozygous for the C526T transition resulting in a new nonsense mutation, which converts Arg176 to a stop codon.
doi:10.1002/ccr3.47
PMCID: PMC4184625  PMID: 25356239
Cockayne syndrome; CSB gene; mutation

Results 1-25 (99)