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1.  Thrombocytopenia for prediction of hepatocellular carcinoma recurrence: Systematic review and meta-analysis 
AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma (HCC).
METHODS: We searched the PubMed, EMBASE, and Web of Science databases to obtain eligible studies. The hazard ratios (HRs) values and 95% confidence intervals (CIs) were pooled by random effects model. Subsequently, we estimated the heterogeneity, performed a sensitivity analysis, determined the publication bias, and performed subgroup and meta-regression analyses. Study quality was assessed by using the Oxford Center for Evidence Based Medicine tool.
RESULTS: We identified 18 eligible studies by retrieval (published during 2000-2014). Out of the 4163 patients with HCC who were recruited, 2746 (66.0%) experienced recurrence. In general, our meta-analysis suggested that low platelet count (PLT) before therapy significantly increased the probability of postoperative recurrence (HR = 1.53, 95%CI: 1.29-1.81). PLT was also valuable in the prediction of intrahepatic distant recurrence (HR = 1.49, 95%CI: 1.25-1.77). Subgroup and meta-regression analyses identified various therapeutic modalities as the source of a high degree of heterogeneity. The pooled HR values showed no obvious change when a single study was removed, but otherwise, an opposite-effects model was used. In addition, no significant publication bias was detected.
CONCLUSION: Thrombocytopenia before treatment might be an inexpensive and useful predictor of postoperative recurrence in patients with HCC.
doi:10.3748/wjg.v21.i25.7895
PMCID: PMC4491977  PMID: 26167090
Hepatocellular carcinoma; Blood platelets; Thrombocytopenia; Recurrence; Prognosis
2.  Prediction models and risk assessment for silicosis using a retrospective cohort study among workers exposed to silica in China 
Scientific Reports  2015;5:11059.
This study aims to develop a prognostic risk prediction model for the development of silicosis among workers exposed to silica dust in China. The prediction model was performed by using retrospective cohort of 3,492 workers exposed to silica in an iron ore, with 33 years of follow-up. We developed a risk score system using a linear combination of the predictors weighted by the LASSO penalized Cox regression coefficients. The model’s predictive accuracy was evaluated using time-dependent ROC curves. Six predictors were selected into the final prediction model (age at entry of the cohort, mean concentration of respirable silica, net years of dust exposure, smoking, illiteracy, and no. of jobs). We classified workers into three risk groups according to the quartile (Q1, Q3) of risk score; 203 (23.28%) incident silicosis cases were derived from the high risk group (risk score ≥ 5.91), whilst only 4 (0.46%) cases were from the low risk group (risk score < 3.97). The score system was regarded as accurate given the range of AUCs (83–96%). This study developed a unique score system with a good internal validity, which provides scientific guidance to the clinicians to identify high-risk workers, thus has important cost efficient implications.
doi:10.1038/srep11059
PMCID: PMC4473532  PMID: 26090590
3.  Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma 
AIM: To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio (PLR) in patients with gallbladder carcinoma (GBC).
METHODS: Clinical data of 316 surgical GBC patients were analyzed retrospectively, and preoperative serum platelet and lymphocyte counts were used to calculate the PLR. The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic (ROC) curve. The primary outcome was overall survival, which was estimated by the Kaplan-Meier method. The log-rank test was used to compare the differences in survival. Then, we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients.
RESULTS: For the PLR, the area under the ROC curve was 0.620 (95%CI: 0.542-0.698, P = 0.040) in detecting death. The cut-off value for the PLR was determined to be 117.7, with 73.6% sensitivity and 53.2% specificity. The PLR was found to be significantly positively correlated with CA125 serum level, tumor-node-metastasis (TNM) stage, and tumor differentiation. Univariate analysis identified carcinoembryonic antigen (CEA), CA125 and CA199 levels, PLR, TNM stage, and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data. Multivariate analysis showed that CA125 > 35 U/mL, CA199 > 39 U/mL, PLR ≥ 117.7, and TNM stage IV were independently associated with poor survival in GBC. When expressed as a continuous variable, the PLR was still an independent predictor for survival, with a hazard ratio of 1.018 (95%CI: 1.001-1.037 per 10-unit increase, P = 0.043).
CONCLUSION: The PLR could be used as a simple, inexpensive, and valuable tool for predicting the prognosis of GBC patients.
doi:10.3748/wjg.v21.i21.6675
PMCID: PMC4458778  PMID: 26074706
Platelets; Lymphocyte; Gallbladder carcinoma; Prognosis; Survival
4.  Influence of mechanical stimulation on human dermal fibroblasts derived from different body sites 
Mechanical stimulation is highly associated with pathogenesis of human hypertrophic scar. Although much work has focused on the influence of mechanical stress on fibroblast populations from various tissues and organs in the human body, their effects on cultured dermal fibroblasts by the area of the body have not been as well studied. In this study, cultures of skin fibroblasts from two different body sites were subjected to cyclic mechanical stimulation with a 10% stretching amplitude at a frequency of 0.1 Hz for 24, 36 and 48 hours, respectively, and thereafter harvested for experimental assays. Fibroblasts from scapular upper back skin, subjected to mechanical loads for 36 and 48 hours, respectively, were observed to proliferate at a higher rate and reach confluent more rapidly during in vitro culturing, had higher expression levels of mRNA and protein production of integrin β1, p130Cas and TGF β1 versus those from medial side of upper arm. These data indicate that skin fibroblasts, with regard to originated body sites studied in the experiments, display a diversity of mechanotransduction properties and biochemical reactions in response to applied mechanical stress, which contributes to the increased susceptibility to hypertrophic scars formation at certain areas of human body characterized by higher skin and muscle tension.
PMCID: PMC4509256  PMID: 26221311
Fibroblasts; body sites; hypertrophic scar; normal skin; mechanical stress
5.  Significance of platelet count and platelet-based models for hepatocellular carcinoma recurrence 
AIM: To explore the effects of platelet count (PLT) and 11 platelet-based indices on postoperative recurrence of hepatocellular carcinoma (HCC).
METHODS: We retrospectively analyzed 172 HCC patients who were treated by partial hepatectomy. Preoperative data, including laboratory biochemical results, were used to calculate the 11 indices included in the analysis. We performed receiver operating characteristic curve analysis to determine the optimal cut-off values for predicting recurrence. Cumulative rates of HCC recurrence were calculated using Kaplan-Meier survival curves and differences were analyzed by log-rank tests. Multivariate analyses were performed to identify independent predictors of recurrence, early recurrence (within one year after surgery), and late recurrence in HCC. To obtain better prognostic models, PLT-based indices were analyzed separately after being expressed as binary and continuous variables. Two platelet-unrelated, validated HCC prognostic models were included in the analyses as reference indices. Additional analyses were performed after patients were stratified based on hepatitis B virus infection status, cirrhosis, and tumor size to investigate the significance of platelets in different subgroups.
RESULTS: In the study cohort, 44.2% (76/172) of patients experienced HCC recurrence, and 50.6% (87/172) died during a median follow-up time of 46 mo. PLT and five of the 11 platelet-related models were significant predisposing factors for recurrence (P < 0.05). Multivariate analysis indicated that, among the clinical parameters, presence of ascites, PLT ≥ 148 × 109/L, alkaline phosphatase ≥ 116 U/L, and tumor size ≥ 5 cm were independently associated with a higher risk of HCC recurrence (P < 0.05). Independent and significant models included the aspartate aminotransferase/PLT index, fibrosis index based on the four factors, fibro-quotient, aspartate aminotransferase/PLT/γ-glutamyl transpeptidase/alpha-fetoprotein index, and the PLT/age/alkaline phosphatase/alpha-fetoprotein/aspartate aminotransferase index. There were different risk factors between early and late recurrences, and PLT and these indices were more inclined to influence late recurrence. PLT was only predictive of recurrence in non-cirrhotic HCC patients, and was not influenced by tumor size, which was a critical confounder in our study.
CONCLUSION: PLT and PLT-based noninvasive models are effective tools for predicting postoperative recurrence, especially late recurrence. Larger cohorts are needed to validate our findings.
doi:10.3748/wjg.v21.i18.5607
PMCID: PMC4427685  PMID: 25987786
Alkaline phosphatase; Alpha-fetoprotein; Aspartate aminotransferase; Blood platelets; Hepatocellular carcinoma; Recurrence
6.  Development of genetically engineered iNKT cells expressing TCRs specific for the M. tuberculosis 38-kDa antigen 
Introduction
The invariant natural killer T (iNKT) cell has been shown to play a central role in early stages immune responses against Mycobacterium tuberculosis (Mtb) infection, which become nonresponsive (anergic) and fails to control the growth of Mtb in patients with active tuberculosis. Enhancement of iNKT cell responses to Mtb antigens can help to resist infection.
Study design and methods
In the present study, an Mtb 38-kDa antigen-specific T cell receptor (TCR) was isolated from human CD8+ T cells stimulated by 38-kDa antigen in vitro, and then transduced into primary iNKT cells by retrovirus vector.
Results
The TCR gene-modified iNKT cells are endowed with new features to behave as a conventional MHC class I restricted CD8+ T lymphocyte by displaying specific antigen recognition and anti-Mtb antigen activity in vitro. At the same time, the engineered iNKT cells retaining its original capacity to be stimulated proliferation by non-protein antigens α-Gal-Cer.
Conclusions
This work is the first attempt to engineer iNKT cells by exogenous TCR genes and demonstrated that iNKT cell, as well as CD4+ and CD8+ T cells, can be genetically engineered to confer them a defined and alternative specificity, which provides new insights into TCR gene therapy for tuberculosis patients, especially those infected with drug-resistant Mtb.
doi:10.1186/s12967-015-0502-4
PMCID: PMC4428004  PMID: 25943357
Mycobacterium tuberculosis (Mtb); iNKT; T cell receptor (TCR); 38-kDa antigen; Gene-modification
7.  Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients 
AIM: To investigate the effects of single nucleotide polymorphisms (SNPs) in glutathione S-transferase (GST) genes on survival of hepatocellular carcinoma (HCC) patients.
METHODS: Twelve tagging SNPs in GST genes (including GSTA1, GSTA4, GSTM2, GSTM3, GSTO1, GSTO2 and GSTP1) were genotyped using Sequenom MassARRAY iPLEX genotyping method in a cohort of 214 Chinese patients with resected HCC. The Cox proportional hazards model and log-rank test were performed to determine the SNPs related to outcome. Additionally, stratified analysis was performed at each level of the demographic and clinical variables. An SNP-gene expression association model was further established to investigate the correlation between SNP and gene expression.
RESULTS: Two SNPs (GSTO2: rs7085725 and GSTP1: rs4147581) were significantly associated with overall survival in HCC patients (P = 0.035 and 0.042, respectively). In stratified analysis, they were more significantly associated with overall survival in patients with younger age, male gender and cirrhosis. We further investigated cumulative effects of these two SNPs on overall survival in HCC patients. Compared with the patients carrying no unfavorable genotypes, those carrying 2 unfavorable genotypes had a 1.70-fold increased risk of death (P < 0.001). The cumulative effects were more significant in those patients with younger age, male gender and cirrhosis (HR = 2.00, 1.94 and 1.97, respectively; all P < 0.001). Additionally, we found that heavy smoking resulted in a significantly worse overall survival in those patients carrying variant alleles of rs7085725 (HR = 2.07, 95%CI: 1.13-3.76, P = 0.018). The distributions of GSTO2: rs7085725 and GSTP1: rs4147581 genotypes were associated with altered gene expression and contributed to influences on overall survival.
CONCLUSION: Our study provides the first evidence that GSTO2 and GSTP1 gene polymorphisms may serve as independent prognostic markers for HCC patients.
doi:10.3748/wjg.v21.i14.4310
PMCID: PMC4394094  PMID: 25892883
Glutathione S-transferase; Polymorphism; Hepatocellular carcinoma; Clinical outcome; Surgery
8.  Endothelial progenitor cells in ischemic stroke: an exploration from hypothesis to therapy 
As the population ages and lifestyles change in concordance, the number of patients suffering from ischemic stroke and its associated disabilities is increasing. Studies on determining the relationship between endothelial progenitor cells (EPCs) and ischemic stroke have become a new hot spot and have reported that EPCs may protect the brain against ischemic injury, promote neurovascular repair, and improve long-term neurobehavioral outcomes. More importantly, they introduce a new perspective for prognosis assessment and therapy of ischemic stroke. However, EPCs’ origin, function, influence factors, injury repair mechanisms, and cell-based therapy strategies remain controversial. Particularly, research conducted to date has less clinical studies than pre-clinical experiments on animals. In this review, we summarized and analyzed the current understanding of basic characteristics, influence factors, functions, therapeutic strategies, and disadvantages of EPCs as well as the regulation of inflammatory factors involved in the function and survival of EPCs after ischemic stroke. Identifying potential therapeutic effects of EPCs in ischemic stroke will be a challenging but an incredibly important breakthrough in neurology, which may bring promise for patients with ischemic stroke.
doi:10.1186/s13045-015-0130-8
PMCID: PMC4446087  PMID: 25888494
Ischemic stroke; Endothelial progenitor cells; Basic characteristics; Influence factors; Function; Therapy; Inflammatory factors; Review
9.  Characterization of the Recognition Specificity of BH2, a Monoclonal Antibody Prepared against the HLA-B27 Heavy Chain 
BH2, a monoclonal antibody prepared against the denatured human leukocytic antigen-B27 heavy chain (HLA-B27 HC), can immunoprecipitate the misfolded HLA-B27 HC complexed with Bip in the endoplasmic reticulum and recognize the homodimerized HLA-B27 HC that is often observed on the cell membrane of patients suffered from ankylosing spondylitis (AS). However, the recognition specificity of BH2 toward the other molecules of HLA-B type and toward the different types of HLA molecules remained uncharacterized. In this study, we carried out the HLA-typing by using the Luminex Technology to characterize the recognition specificity of BH2 and analyzed the binding domain of HLA-B27 HC by BH2. Our results indicated that BH2 preferably binds to molecules of HLA-B and -C rather than HLA-A and the binding site is located within the α2 domain of HLA-B27 HC.
doi:10.3390/ijms16048142
PMCID: PMC4425072  PMID: 25872138
HLA-B27; ankylosing spondylitis; monoclonal antibody; HLA-typing
10.  Retinoid X receptor α attenuates host antiviral response by suppressing type I interferon 
Nature communications  2014;5:5494.
The retinoid X receptor α (RXRα), a key nuclear receptor in metabolic processes, is down-regulated during host antiviral response. However, the roles of RXRα in host antiviral response are unknown. Here we show that RXRα overexpression or ligand activation increases host susceptibility to viral infections in vitro and in vivo, while Rxra −/− or antagonist treatment reduces infection by the same viruses. Consistent with these functional studies, ligand activation of RXR inhibits the expression of antiviral genes including type I interferon (IFN) and Rxra −/− macrophages produce more IFNβ than WT macrophages in response to polyI:C stimulation. Further results indicate that ligand activation of RXR suppresses the nuclear translocation of β-catenin, a co-activator of IFNβ enhanceosome. Thus, our studies have uncovered a novel RXR-dependent innate immune regulatory pathway, suggesting that the downregulation of RXR expression or RXR antagonist treatment benefits host antiviral response, whereas RXR agonist treatment may increase the risk of viral infections.
doi:10.1038/ncomms6494
PMCID: PMC4380327  PMID: 25417649
11.  Construction of a CXCL12-KDEL Fusion Gene to Inhibit Head and Neck Squamous Cell Carcinoma Metastasis by Intracellular Sequestration of CXCR4 
BioMed Research International  2015;2015:195828.
The CXCL12-CXCR4 biological axis consisting of the chemotactic factor CXCL12 and its specific receptor CXCR4 plays an important role in oral cancer metastasis. High expression of CXCR4 may help oral squamous cancer cells invade local tissues and metastasize to lymph nodes. No obvious association was observed between CXCL12 expression and lymph node metastasis, suggesting that CXCL12 chemotaxis may only be related to CXCR4 expression on the tumor cell membrane. KDEL can be retained by receptors on the surface of the intracellular endoplasmic reticulum (ER) and also be called an ER retention signal sequence. So we adopted the KDEL sequence in this study to generate a CXCL12-KDEL fusion protein in combination with a traceable E-tag label. As such, CXCL12 was retained in the ER. Specific receptor CXCR4 binds to the CXCL12-KDEL, was also retained in the ER, and was thus prevented from reaching the oral squamous cancer cell surface. We reduced the cell surface level of CXCR4 and called the technique “intracellular sequestration.” By this way, we have finished blocking of CXCL12-CXCR4 biological axis and inhibiting lymph node metastasis of oral carcinoma.
doi:10.1155/2015/195828
PMCID: PMC4383411  PMID: 25866764
12.  Central obesity and nonalcoholic fatty liver disease risk after adjusting for body mass index 
AIM: To investigate whether central obesity is associated with nonalcoholic fatty liver disease (NAFLD) formation after adjusting for general obesity.
METHODS: The online databases PubMed, EMBASE, and ISI Web of Science were searched for studies estimating the influence of central obesity on NAFLD occurrence published through April 2014. Studies that did not adjust for body mass index (BMI) were excluded. In addition, the independent effect of BMI was also assessed with the included studies. The pooled effect sizes and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models based on the degree of heterogeneity. Furthermore, subgroup analyses, meta-regression, sensitivity analyses, and publication bias were performed.
RESULTS: Twenty eligible studies were identified. The summary odds ratio (OR) values per-unit increase in waist circumference (WC) and BMI for NAFLD formation were 1.07 (95%CI: 1.03-1.10, I2 = 73.9%, n = 11 studies) and 1.25 (95%CI: 1.13-1.38, I2 = 88.7%, n = 11 studies), respectively. When the indices were expressed as binary variables (with the non-obesity group as reference), the pooled OR in WC, waist-to-hip ratio, and BMI were 2.34 (95%CI: 1.83-3.00, I2 = 41.8%, n = 7 studies), 4.06 (95%CI: 1.53-10.79, I2 = 65.7%, n = 3 studies), and 2.85 (95%CI: 1.60-5.08, I2 = 57.8%, n = 5 studies), respectively. Using the same studies as the latter (n = 5), pooled OR in WC was 3.14 (95%CI: 2.07-4.77), which is greater than that in BMI.
CONCLUSION: Central obesity may pose a greater threat to national health than general obesity, although both are independently associated with increased risk of NAFLD.
doi:10.3748/wjg.v21.i5.1650
PMCID: PMC4316109  PMID: 25663786
Central obesity; General obesity; Nonalcoholic fatty liver disease; Body mass index; Waist circumference
13.  Characterizing the Temporal Dynamics of Human Papillomavirus DNA Detectability Using Short-Interval Sampling 
Background
Variable detection of human papillomavirus (HPV) DNA can result in misclassification of infection status, but the extent of misclassification has not been quantitatively evaluated.
Methods
In 2005–2007, 33 women aged 22–53 self-collected vaginal swabs twice per week for 16 consecutive weeks. Each of the 955 swabs collected was tested for 37 HPV types/subtypes. Assuming that a woman’s underlying infection status did not change over the short study period, biases in prevalence estimates obtained from single versus multiple swabs were calculated. Using event history analysis methods, time to recurrent gain and loss of at least one HPV type was determined, separately. Baseline any- and high risk-HPV prevalence was 60.6% and 24.2%, respectively. Cumulative any- and high risk-HPV prevalence over the 16-week period was 84.8% and 60.6%, separately.
Results
Overall, there were 319 events of detection and 313 events of loss of detection. Median times to a recurrent detection and loss of detection was 11 and 7 days, respectively. Neither vaginal sex nor condom use during follow-up was associated with recurrent viral detection or loss of detection. Assuming the cumulative 16-week prevalence reflects the true prevalence of infection, the baseline any-HPV prevalence under-estimated infection status by 24.2%, with a bootstrapped mean of 20.2% (95% confidence interval [CI]: 8.9%, 29.6%).
Conclusions
These findings suggest that a substantial proportion of HPV-infected women are misclassified as being un-infected when using a single-time DNA measurement.
Impact
Short-term variation in detectable HPV DNA needs to be considered while interpreting the natural history of infections using single samples collected at long intervals.
doi:10.1158/1055-9965.EPI-13-0666
PMCID: PMC3947138  PMID: 24130223
Epidemiology; Human papillomavirus; Interval sampling; Misclassification bias; Prevalence
14.  Arsenic induces diabetic effects through beta-cell dysfunction and increased gluconeogenesis in mice 
Scientific Reports  2014;4:6894.
Arsenic as a potential risk factor for type 2 diabetes has been received attention recently. However, the roles of arsenic on development of diabetes are unclear. In this study, we compared the influences of inorganic arsenic (iAs) on normal and diabetic mice by systems toxicology approaches. Although iAs exposure did not change glucose tolerance in normal mice, it caused the pancreatic β-cell dysfunction and increased gluconeogenesis and oxidative damages in liver. However, iAs exposure worsened the glucose tolerance in diabetic mice, which might be due to increased gluconeogenesis and impairment of pancreatic β-cell function. It is interesting that iAs exposure could improve the insulin sensitivity based on the insulin tolerance testing by the activation of glucose uptake-related genes and enzymes in normal and diabetic individuals. Our data suggested that iAs exposure could cause pre-diabetic effects by altering the lipid metabolism, gluconeogenesis and insulin secretion in normal individual, and worsen diabetic effects in diabetes individual by these processes. Insulin resistance might be not the reason of diabetic effects caused by iAs, indicating that mechanism of the diabetogenic effects of iAs exposure is different from the mechanism associated with traditional risk factors (such as obesity)-reduced type 2 diabetes.
doi:10.1038/srep06894
PMCID: PMC4219158  PMID: 25367288
15.  Menstrual Cycle and Detectable Human Papillomavirus in Reproductive-age Women: A Time Series Study 
The Journal of Infectious Diseases  2013;208(9):1404-1415.
Background. Current evidence on the relationship between human papillomavirus (HPV) DNA detection and menstrual cycle has been inconsistent.
Methods. We included 21 nonoral contraceptive pill (non-OCP) users who self-collected vaginal samples twice per week for 16 weeks. We explored whether variable detection of HPV DNA exhibited cyclic or other structured temporal patterns. We also evaluated relationships between serial HPV prevalence, sexual behavior, and suspected bacterial vaginosis (BV) as defined by Nugent Gram stain score ≥7.
Results. During follow-up, any-type HPV prevalence varied between 61.1% and 85.0%. Although not statistically significant, we observed a maximum autocorrelation in serial HPV prevalence lagging 14 days (correlation coefficient [ρ], −0.24). Any-type HPV detection had a periodic behavior, generally repeating every 28.0 days (bootstrapped interquartile range, 22.4–28.0) and peaking around the ovulation time (adjusted odds ratio, 1.96; 95% confidence interval [CI], 1.06–3.62) as compared to menstruation. We also showed that an increase in any-type HPV prevalence preceded the beginning of a menstrual cycle by 9–12 days. There was no evidence of relationships between HPV prevalence and sexual activity or Nugent score.
Conclusions. Serially detected any-type HPV DNA showed a periodic behavior and was likely to peak in the periovulatory phase among non-OCP users.
doi:10.1093/infdis/jit337
PMCID: PMC3789568  PMID: 23885113
Auto-correlation; Bacterial Vaginosis; Human Papillomavirus; Menstrual Cycle; Nugent Score; Periodicity; Spectral Analysis; Time Series Analysis
16.  WISH/DIP/SPIN90 proteins form a class of Arp2/3 complex activators that function without preformed actin filaments 
Current biology : CB  2013;23(20):1990-1998.
Background
Arp2/3 complex is a key actin cytoskeletal regulator that creates branched actin filament networks in response to cellular signals. WASP-activated Arp2/3 complex assembles branched actin networks by nucleating new filaments from the sides of pre-existing ones. WASP-mediated activation requires seed filaments, to which the WASP-bound Arp2/3 complex can bind to form branches, but the source of the first substrate filaments for branching is unknown.
Results
Here we show that Dip1, a member of the WISH/DIP/SPIN90 family of actin regulators, potently activates Arp2/3 complex without preformed filaments. Unlike other Arp2/3 complex activators, Dip1 does not bind actin monomers or filaments, and interacts with the complex using a non-WASP-like binding mode. In addition, Dip1-activated Arp2/3 complex creates linear instead of branched actin filament networks.
Conclusions
Our data show the mechanism by which Dip1 and other WISH/DIP/SPIN90 proteins can provide seed filaments to Arp2/3 complex to serve as master switches in initiating branched actin assembly. This mechanism is distinct from other known activators of Arp2/3 complex.
doi:10.1016/j.cub.2013.08.029
PMCID: PMC3930447  PMID: 24120641
17.  Compound Danshen Dripping Pill Pretreatment to Prevent Contrast-Induced Nephropathy in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention 
Background. Contrast-induced nephropathy (CIN) limits the outcome of percutaneous coronary intervention (PCI). Objective. To investigate whether pretreatment with Compound Danshen Dripping Pills (CDDP) will decrease the incidence of CIN after PCI. Methods. A total of 229 patients with acute coronary syndrome (ACS) undergoing PCI were divided into the control group (n = 114) and the CDDP (containing salvia miltiorrhiza and sanqi) group (n = 115; given 20 CDDP pills, three times daily before PCI). Serum creatinine, creatinine clearance (CrCl), high-sensitivity C-reactive protein (hsCRP), P-selectin, and intercellular adhesion molecule-1 (ICAM-1) were measured at admission and 24 and 48 h after PCI. Results. CrCl decreased after PCI but recovered after 48 h. In the CDDP group, CrCl recovered more rapidly (P < 0.05). The procedure increased the hsCRP, P-selectin, and ICAM-1 levels, but these levels were less in the CDDP group (P < 0.05). Conclusions. Pretreatment with CDDP can decrease the occurrence of CIN in patients undergoing PCI, suggesting that the early use of CDDP is an appropriate adjuvant pharmacological therapy before PCI.
doi:10.1155/2014/256268
PMCID: PMC4216665  PMID: 25386219
18.  Obesity and Human Papillomavirus Infection in Perimenopausal Women 
The Journal of Infectious Diseases  2013;208(7):1071-1080.
Introduction. Obesity is known to increase susceptibility to certain infections in men. It is unclear whether obesity increases women's risk for human papillomavirus (HPV) infection.
Methods. In a prospective cohort of 696 perimenopausal women enrolled in 2008–2012, we sought to determine whether obesity predicted incident HPV detection or nondetection. Obesity was defined as body mass index (BMI) ≥ 30 kg/m2.
Results. Baseline any type HPV prevalence was comparable between obese and nonobese women (18.7% vs 19.1%; P > .05). Over a median follow-up period of 17.9 months (interquartile range: 12.1–24.5), 187 new HPV detections occurred among 123 women, 60 of whom subsequently lost 76 detectable infections. When compared with nonobese participants, obese women had a similar rate of new HPV detection (7.1 vs 7.8 infections per 1000 infection-years; P > .05) or loss of detection (100.3 vs 85.8 infections per 100 infection-years; P > .05). Similar results were found after adjusting for age, menopausal status, smoking habit, and sexual exposure history.
Conclusions. Results from the current analysis suggest little effect of obesity on HPV detection and loss of detection in mid-adult women. More research is needed to determine whether adipokines or cytokines better capture the potential immune modulating effects of obesity on HPV infection.
doi:10.1093/infdis/jit297
PMCID: PMC3762384  PMID: 23840046
adipokine; body mass index; discrete-time survival analysis; frailty model; human papillomavirus; obesity; waist circumference
19.  Oral contraceptive pill use is associated with reduced odds of nonalcoholic fatty liver disease in menstruating women: results from NHANES III 
Journal of gastroenterology  2012;48(10):1151-1159.
Background
Higher prevalence of nonalcoholic fatty liver disease (NAFLD) in men and postmenopausal women than in premenopausal women has suggested a potential role of sex hormones in the pathogenesis of the disease. We sought to evaluate the association between oral contraceptive pills (OCP) and NAFLD and to determine whether adiposity mediates any effect.
Methods
We included 4338 women aged 20–60 years who were enrolled in the Third National Health and Nutrition Examination Survey from 1988 to 1994 in a population-based cross-sectional study. We defined NA-FLD as moderate–severe steatosis on ultrasonography in women without excessive alcohol use or other identifiable causes. OCP use was based on self-report and was categorized as never, former or current use.
Results
The overall weighted prevalence of NAFLD was 11.6 % but lower in current (6.7 %) than in former (12.0 %) or never users (15.6 %, P = 0.016). In the multivariable model, current OCP users experienced a 50 % lower odds of NAFLD than never users (adjusted odds ratio 0.50; 95 % confidence interval 0.26, 0.98) after adjusting for age, race/ethnicity, smoking status, history of diabetes or hypertension and education. Further adjustment for body mass index or waist circumference significantly attenuated the OCP–NAFLD relationship.
Conclusions
In this large US-representative population, OCP use was associated with reduced odds of NAFLD. However, this association could be mediated or confounded by adiposity. Prospective studies are needed to further clarify the causal role of sex hormone.
doi:10.1007/s00535-012-0715-8
PMCID: PMC4170913  PMID: 23188092
Adiposity; Nonalcoholic fatty liver disease; Obesity; Oral contraceptive pill; Sex hormone
20.  Clinical Features and Molecular Analysis of Hb H Disease in Taiwan 
BioMed Research International  2014;2014:271070.
Thalassemia is highly prevalent in Taiwan, but limited data are available about the association between genotypes and clinical manifestations in Taiwanese patients with Hb H disease. Here, we studied α-globin gene abnormalities and clinical features in Taiwanese patients with Hb H disease. Of the 90 patients, sixty-four (71.1%) were deletional and twenty-six (28.9%) were nondeletional Hb H disease. The (- -SEA) type of α0-thalassemia mutation was detected in the majority of patients (>95%). The most common genotype was (- -SEA/-α3.7), followed by (- -SEA/αcsα). After further investigation of the genotype-phenotype correlation in 68 patients, we found that patients with nondeletional Hb H disease had more severe clinical features than those with deletional Hb H disease, including younger age at diagnosis, more requirement of blood transfusions, and larger proportion of patients with splenomegaly, hepatomegaly or jaundice. This is probably a consequence of the lower hemoglobin levels and the higher Hb H levels. The clinical severity was highly variable even among patients with an identical genotype, and the diversity was much more profound among patients with (- -/αcsα) genotype. Therefore, predicting the phenotype directly from the genotype in Hb H disease remains relatively difficult in Taiwan.
doi:10.1155/2014/271070
PMCID: PMC4163353  PMID: 25309906
21.  Berberine suppresses in vitro migration of human aortic smooth muscle cells through the inhibitions of MMP-2/9, u-PA, AP-1, and NF-κB 
BMB Reports  2014;47(7):388-392.
Berberine, a type of isoquinoline alkaloid isolated from Chinese medicinal herbs, has been reported to have various pharmacological activities. Studies have demonstrated that berberine has beneficial effects on vascular remodeling and alleviates restenosis after vascular injury. However, its mechanism of action on vascular smooth muscle cell migration is not fully understood. We therefore investigated the effect of berberine on human aortic smooth muscle cell (HASMC) migration. Boyden chamber assay was performed to show that berberine inhibited HASMC migration dosedependently. Real-time PCR and Western blotting analyses showed that levels of matrix metalloproteinase (MMP)-2, MMP-9, and urokinase-type plasminogen activator (u-PA) were reduced by berberine at both the mRNA and protein levels. Western blotting assay further confirmed that activities of c-Fos, c-Jun, and NF-κB were significantly attenuated. These results suggest that berberine effectively inhibited HASMC migration, possibly by down-regulating MMP-2, MMP-9, and u-PA; and interrupting AP-1 and NF-κB mediated signaling pathways. [BMB Reports 2014; 47(7): 388-392]
doi:10.5483/BMBRep.2014.47.7.186
PMCID: PMC4163851  PMID: 24286329
Berberine; Human aortic smooth muscle cells; Matrix metalloproteinase; Migration; Restenosis
22.  Clinical characteristics of 26 patients with primary extranodal Hodgkin lymphoma 
Background: Most Hodgkin lymphoma (HL) patients present with disease in nodal regions. However, in a small subset, disease develops extranodal sites primarily, such as lung and liver. This study aims to identify the characteristics and outcomes of patients with primary extranodal HL. Methods: A retrospective analysis of patients with HL from 1998 to 2012 was enrolled. We selected 26 HL patients with primary extranodal involvement from 251 previously untreated HL patients. All data analyses were performed with SPSS software version 17.0 and GraphPad Prism 5. Results: We identified 26 patients with primary extranodal HL. Results in the series of young patients, male predominated. Pathologically, the major pathologic types were nodular sclerosis classical HL (NSCHL, 46.2%) and mixed cellularity classical HL (MCCHL, 38.5%). Thirteen patients had early stage (I or II stage). The most commonly primarily extranodal sites were the lung and the stomach and intestine, followed by the liver and bones. Fifteen of 26 received chemotherapy alone and 11 received combination therapy. Finally, primary extranodal HLs in our study have a favorable survival. Furthermore, there was no significant association between the international prognostic score (IPS) and survival in patients with extranodal HL. Conclusion: Our retrospective data in part reflect clinical characteristics of primary extranodal HL in China, and form the basis for further concerning researches.
PMCID: PMC4152067  PMID: 25197377
Hodgkin’s lymphoma; extranodal; prognosis; international prognostic score; survival; 18F-FDGPET-CT
23.  Effects of Dimethylaminoethanol and Compound Amino Acid on D-Galactose Induced Skin Aging Model of Rat 
The Scientific World Journal  2014;2014:507351.
A lasting dream of human beings is to reverse or postpone aging. In this study, dimethylaminoethanol (DMAE) and compound amino acid (AA) in Mesotherapy were investigated for their potential antiaging effects on D-galactose induced aging skin. At 18 days after D-gal induction, each rat was treated with intradermal microinjection of saline, AA, 0.1% DMAE, 0.2% DMAE, 0.1% DMAE + AA, or 0.2% DMAE + AA, respectively. At 42 days after treatment, the skin wound was harvested and assayed. Measurement of epidermal and dermal thickness in 0.1% DMAE + AA and 0.2% DMAE + AA groups appeared significantly thicker than aging control rats. No differences were found in tissue water content among groups. Hydroxyproline in 0.1% DMAE + AA, 0.2% DMAE + AA, and sham control groups was much higher than all other groups. Collagen type I, type III, and MMP-1 expression was highly upregulated in both 0.1% DMAE + AA and 0.2% DMAE + AA groups compared with aging control. In contrast, TIMP-1 expression levels of various aging groups were significantly reduced when compared to sham control. Coinjection of DMAE and AA into target tissue has marked antiaging effects on D-galactose induced skin aging model of rat.
doi:10.1155/2014/507351
PMCID: PMC4123624  PMID: 25133239
24.  Happy@Work: protocol for a web-based randomized controlled trial to improve mental well-being among an Asian working population 
BMC Public Health  2014;14:685.
Background
Mental health issues pose a serious concern in the workplace for the huge productivity loss and financial burden associated with it. Unlike the traditional ‘fixing-what-is-wrong’ approach, positive psychology offers a less-stigmatized way to promote mental health. Psychological capital, a concept originated from positive psychology, has been proven effective in improving mental well-being and work performance. However, little evidence exists for its implementation among Asian working population or its cost-benefit for organizations adopting such promotion strategy. The current study is designed to assess the protective effects of a web-based psychology capital intervention among Hong Kong working population on individuals’ mental health and work performance, as well as organizations’ return-on-investment.
Methods/Design
A two-arm randomized controlled trial design will be adopted. Eligible working adults will be randomly allocated to either the intervention group or the waiting-list control group, with 177 participants in each arm. The intervention, which consists of four web-based training sessions, each targeting one of the psychological capital components (hope, efficacy, optimism and resilience), will be implemented over a 4-week period. On-line surveys will assess the participants in each group at baseline, intervention completion, 1 and 3 months after the completion. The primary outcome is individuals’ psychological capital level; secondary outcomes include individuals’ well-being, depressive symptoms, work engagement and productivity. Return-on-investment will be calculated from the employers’ perspective based on productivity gain, savings in medical expenditure, as well as operation and time costs. Analysis will follow the intention-to-treat principle.
Discussion
This is the first experimental study that explores the applicability of psychological capital development among Asian population. Through investigating changes in individuals’ work productivity from absenteeism and presenteeism, this will be one of the few studies that quantify productivity gains from any type of mental health promotion. By demonstrating effectiveness in improving mental well-being and a positive return-on-investment rate, the study may help convince more uptake of similar positive psychology interventions at workplace in Asia and elsewhere.
Trail Registration
Number (assigned by Centre for Clinical Trials, Clinical Trials Registry, The Chinese University of Hong Kong): CUHK_CCT00396. Registration Date: 2014/02/13
doi:10.1186/1471-2458-14-685
PMCID: PMC4096423  PMID: 24997007
Mental health; Promotion; Positive psychology; Psychological capital; Return-on-investment; Working population; Hong Kong
25.  Using Benthic Macroinvertebrate and Fish Communities as Bioindicators of the Tanshui River Basin Around the Greater Taipei Area — Multivariate Analysis of Spatial Variation Related to Levels of Water Pollution 
After decades of strict pollution control and municipal sewage treatment, the water quality of the Tanshui River increased significantly after pollution mitigation as indicated by the River Pollution Index (RPI). The pollution level of the estuarine region decreased from severe pollution to mostly moderately impaired. The most polluted waters are presently restricted to a flow track length between 15–35 km relative to the river mouth. From July 2011 to September 2012, four surveys of fish and benthic macroinvertebrates were conducted at 45 sampling sites around the Tanshui River basin. The pollution level of all the study area indicated by the RPI could also be explained by the Family Biotic Index (FBI) and Biotic Index (BI) from the benthic macroinvertebrate community, and the Index of Biotic Integrity (IBI) of the fish community. The result of canonical correlation analysis between aquatic environmental factors and community structure indicated that the community structure was closely related to the level of water pollution. Fish species richness in the estuarine area has increased significantly in recent years. Some catadromous fish and crustaceans could cross the moderate polluted water into the upstream freshwater, and have re-colonized their populations. The benthic macroinvertebrate community relying on the benthic substrate of the estuarine region is still very poor, and the water layer was still moderately polluted.
doi:10.3390/ijerph110707116
PMCID: PMC4113864  PMID: 25026081
bioindicator; benthic invertebrate; fish community; water quality

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