Development of Prediction Model to Estimate the Risk of Heart Failure in Diabetes Mellitus.

Background: Heart failure (HF) is a leading cause of mortality and disability in patients with diabetes mellitus (DM). The aim of the study is to predict the risk of HF incidence in patients with DM by developing a risk prediction model. Methods: We constructed a regression model based on 270 inpatients with DM between February 2018 and January 2019. Binary logistic regression was applied to develop the final model incorporating the predictors selected by least absolute shrinkage and selection operator regression. The nomogram was estimated with an area under the receiver operator characteristic curve and calibration diagram and validated with the bootstrap method. Results: Risk factors including age, coronary heart disease (CHD), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were incorporated in the final model as predictors. Age ≥ 61 years old, LDL, and CHD were risk factors for DM with HF, with odds ratios (ORs) of 32.84 (95% CI: 6.74, 253.99), 1.33 (95% CI: 1.06, 1.72), and 3.94 (95% CI: 1.43, 13.43), respectively. HDL was a protective factor with an OR of 0.11 (95% CI: 0.04, 0.28). The area under curve of the model was 0.863 (95% confidence interval, 0.812∼0.913). The plot of the calibration showed that there was a good consistency between predicted probability and actual probability. Harrell's C-index of the nomogram was 0.845, and the model showed satisfactory calibration in the internal validation cohort. Conclusion: The prediction nomogram we developed can estimate the possibility of HF in patients with DM according the predictor items.

Evaluation of Lipoprotein-Associated Phospholipase A2 as a Prognostic Biomarker in Chronic Kidney Disease.

BACKGROUND: The leading cause of death in patients with chronic kidney disease (CKD) is atherosclerosis (AS). Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a biomarker of atherosclerotic plaque stability. The aim of our study was to analyze the association of Lp-PLA2 with CKD complicated with carotid atherosclerotic stenosis (CAS). METHODS: Serum specimens were collected from 77 CKD patients and 39 healthy controls. Laboratory examination results including glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and Lp-PLA2 were measured. Receiver operating characteristic (ROC) was drawn and the area under the curve (AUC) was calculated. RESULTS: Multivariate logistic regression analysis showed that age, gender, glucose, and Lp-PLA2 were considered as risks for CKD-CAS with odds ratios (OR) of 1.111 (95% CI: 1.055, 1.170), 5.123 (95% CI: 1.482, 17.714), 1.679 (95% CI: 1.123, 2.512), and 1.023 (95% CI: 1.008, 1.037), respectively. The AUC for Lp-PLA2 and glucose was 0.618 (p = 0.014) and 0.592 (p = 0.057), respectively. The best diagnostic value was archived by Lp-PLA2 with the cutoff value of 201.06 ng/mL. CONCLUSIONS: Lp-PLA2 is a potential prognostic and diagnostic biomarker for CKD-CAS.

Identification of an m6A-Related Signature as Biomarker for Hepatocellular Carcinoma Prognosis and Correlates with Sorafenib and Anti-PD-1 Immunotherapy Treatment Response.

BACKGROUND: N6-methyladenosine (m6A) modification plays an essential role in diverse key biological processes and may take part in the development and progression of hepatocellular carcinoma (HCC). Here, we systematically analyzed the expression profiles and prognostic values of 13 widely reported m6A modification-related genes in HCC. METHODS: The mRNA expression of 13 m6A modification-related genes and clinical parameters of HCC patients were downloaded from TCGA, ICGC, GSE109211, and GSE78220. Univariate and LASSO analyses were used to develop risk signature. Time-dependent ROC was performed to assess the predictive accuracy and sensitivity of risk signature. RESULTS: FTO, YTHDC1, YTHDC2, ALKBH5, KIAA1429, HNRNPC, METTL3, RBM15, YTHDF2, YTHDF1, and WTAP were significantly overexpressed in HCC patients. YTHDF1, HNRNPC, RBM15, METTL3, and YTHDF2 were independent prognostic factors for OS and DFS in HCC patients. Next, a risk signature was also developed and validated with five m6A modification-related genes in TCGA and ICGC HCC cohort. It could effectively stratify HCC patients into high-risk patients with shorter OS and DFS and low-risk patients with longer OS and DFS and showed good predictive efficiency in predicting OS and DFS. Moreover, significantly higher proportions of macrophages M0 cells, neutrophils, and Tregs were found to be enriched in HCC patients with high risk scores, while significantly higher proportions of memory CD4 T cells, gamma delta T cells, and naive B cells were found to be enriched in HCC patients with low scores. Finally, significantly lower risk scores were found at sorafenib treatment responders and anti-PD-1 immunotherapy responders compared to that in nonresponders, and anti-PD-1 immunotherapy-treated patients with lower risk scores had better OS than patients with higher risk scores. CONCLUSION: A risk signature developed with the expression of 5 m6A-related genes could improve the prediction of prognosis of HCC and correlated with sorafenib treatment and anti-PD-1 immunotherapy response.

Molecular Epidemiology and Clone Transmission of Carbapenem-Resistant Acinetobacter baumannii in ICU Rooms.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major cause of nosocomial infections and hospital outbreaks worldwide, remaining a critical clinical concern. Here we characterized and investigated the phylogenetic relationships of 105 CRAB isolates from an intensive care unit from one hospital in China collected over six years. All strains carried blaOXA-23 , blaOXA-66 genes for carbapenem resistance, also had high resistance gene, virulence factor, and insertion sequence burdens. Whole-genome sequencing revealed all strains belonged to ST2, the global clone CC2. The phylogenetic analysis based on the core genome showed all isolates were dominated by a single lineage of three clusters and eight different clones. Two clones were popular during the collection time. Using chi-square test to identify the epidemiologically meaningful groupings, we found the significant difference in community structure only existed in strains from separation time. The haplotype and median-joining network analysis revealed genetic differences appeared among clusters and changes occurred overtime in the dominating cluster. Our results highlighted substantial multidrug-resistant CRAB burden in the hospital ICU environment demonstrating potential clone outbreak in the hospital.

Progress on the Mechanism for Aspirin's Anti-tumor Effects.

Since its discovery more than 100 years ago, aspirin has been widely used for its antipyretic, analgesic, anti-inflammatory, and anti-rheumatic activities. In addition to these applications, it is increasingly becoming clear that the drug also has great potential in the field of cancer. Here, we briefly review the current insights on aspirin's anti-tumor effects. These are multiple and vary from inhibiting the major cellular mTOR pathways, acting as a calorie-restricted mimetic by inhibition of energy production, suppressing platelet aggregation and granule release, inhibiting the immune escape of tumor cells, to decreasing inflammatory responses. We consider these five mechanisms of action the most significant for aspirin's anti-tumor effects, whereby the anti-tumor effect may ultimately stem from its inhibition of energy metabolism, platelet function, and inflammatory response. As such, aspirin can play an important role to reduce the occurrence, proliferation, and metastasis of various types of tumors. However, most of the collected data are still based on epidemiological investigations. More direct and effective evidence is needed, and the side effects of aspirin intake need to be solved before this drug can be widely applied in cancer treatment.

Prevalence and Distribution Characteristics of blaKPC-2 and blaNDM-1 Genes in Klebsiella pneumoniae.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae infections have caused major concern and posed a global threat to public health. As blaKPC-2 and blaNDM-1 genes are the most widely reported carbapenem resistant genes in K. pneumonia, it is crucial to study the prevalence and geographical distribution of these two genes for further understanding of their transmission mode and mechanism. PURPOSE: Here, we investigated the prevalence and distribution of blaKPC-2 and blaNDM-1 genes in carbapenem-resistant K. pneumoniae strains from a tertiary hospital and from 1579 genomes available in the NCBI database, and further analyzed the possible core structure of blaKPC-2 or blaNDM-1 genes among global genome data. MATERIALS AND METHODS: K. pneumoniae strains from a tertiary hospital in China during 2013-2018 were collected and their antimicrobial susceptibility testing for 28 antibiotics was determined. Whole-genome sequencing of carbapenem-resistant K. pneumoniae strains was used to investigate the genetic characterization. The phylogenetic relationships of these strains were investigated through pan-genome analysis. The epidemiology and distribution of blaKPC-2 and blaNDM-1 genes in K. pneumoniae based on 1579 global genomes and carbapenem-resistant K. pneumoniae strains from hospital were analyzed using bioinformatics. The possible core structure carrying blaKPC-2 or blaNDM-1 genes was investigated among global data. RESULTS: A total of 19 carbapenem-resistant K. pneumoniae were isolated in a tertiary hospital. All isolates had a multi-resistant pattern and eight kinds of resistance genes. The phylogenetic analysis showed all isolates in the hospital were dominated by two lineages composed of ST11 and ST25, respectively. ST11 and ST25 were the major ST type carrying blaKPC-2 and blaNDM-1 genes, respectively. Among 1579 global genomes data, 147 known ST types (1195 genomes) have been identified, while ST258 (23.6%) and ST11 (22.1%) were the globally prevalent clones among the known ST types. Genetic environment analysis showed that the ISKpn7-dnaA/ISKpn27 -blaKPC-2-ISkpn6 and blaNDM-1-ble-trpf-nagA may be the core structure in the horizontal transfer of blaKPC-2 and blaNDM-1 , respectively. In addition, DNA transferase (hin) may be involved in the horizontal transfer or the expression of blaNDM-1 . CONCLUSION: There was clonal transmission of carbapenem-resistant K. pneumoniae in the tertiary hospital in China. The prevalence and distribution of blaKPC-2 and blaNDM-1 varied by countries and were driven by different transposons carrying the core structure. This study shed light on the genetic environment of blaKPC-2 and blaNDM-1 and offered basic information about the mechanism of carbapenem-resistant K. pneumoniae dissemination.

A prospective cohort study of home blood pressure monitoring based on an intelligent cloud platform (the HBPM-iCloud study): rationale and design.

BACKGROUND: Hypertension, as a predominant risk factor for cardiovascular disease, is a severe public health burden in China. Home blood pressure monitoring (HBPM) is an important tool in the detection and management of hypertension. However, there is a lack of HBPM data from prospective cohorts in China. Hence, we designed this study to investigate the impact of HBPM on major health outcomes in Chinese population participating in regular health check-ups. METHODS: Leveraging telemedicine technology, the open prospective, multicenter, HBPM-iCloud (Home Blood Pressure Monitoring Based on an Intelligent Cloud Platform) cohort study will recruit participants from three participating health check-up centers in southern China to participate in cloud-based HBPM for 1 week. The prevalence of sustained hypertension, white coat hypertension (WCH), masked hypertension (MH), white coat uncontrolled hypertension (WUCH), and masked uncontrolled hypertension (MUCH) will be defined by a combination of average readings of home-based and office-based blood pressure (BP). Cardiovascular risk factors and subclinical target organ damage will be recorded. Participants will be followed-up for 5 years to examine the incidence and associated risk factors of composite major adverse cardiovascular and cerebrovascular event. CONCLUSION: The study will help to determine the best way to implement telemedicine technology in BP control for better prevention and treatment of hypertension. Results will provide data for a Chinese population to aid in the construction of screening, risk stratification, and intervention strategies for abnormal BP phenotypes, including WCH, MH, WUCH, and MUCH.

Secreted Frizzled-Related Protein 2 and Extracellular Volume Fraction in Patients with Heart Failure.

BACKGROUND: Quantification of extracellular volume (ECV) fraction by cardiovascular magnetic resonance (CMR) has emerged as a noninvasive diagnostic tool to assess myocardial fibrosis. Secreted frizzled-related protein 2 (SFRP2) appears to play an important role in cardiac fibrosis. We aimed to evaluate the association between SFRP2 and myocardial fibrosis and the prognostic value of ECV fraction in patients with heart failure (HF). METHODS: In this prospective cohort study, 72 hospitalized adult patients (age ≥ 18 years) with severe decompensated HF were included. CMR measurements and T1 mapping were performed to calculate ECV fraction. Serum SFRP2 level was detected by an enzyme-linked immunosorbent assay kit. All patients were followed up, and the primary outcomes were composite events including all-cause mortality and HF hospitalization. RESULTS: During the median follow-up of 12 months, 27 (37.5%) patients experienced primary outcome events and had higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), SFRP2, and ECV fraction compared with those without events. In Pearson correlation analysis, levels of SFRP2 (r = 0.33), high-sensitivity C-reactive protein (r = 0.31), and hemoglobin A1c (r = 0.29) were associated with ECV fraction (all P < 0.05); however, in multivariate linear regression analysis, SFRP2 was the only significant factor determined for ECV fraction (r partial = 0.33, P = 0.02). In multivariate Cox regression analysis, age (each 10 years, hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.04-1.22), ECV fraction (per doubling, HR 1.68, 95% CI 1.03-2.74), and NT-proBNP (per doubling, HR 2.46, 95% CI 1.05-5.76) were independent risk factors for primary outcomes. CONCLUSIONS: Higher ECV fraction is associated with worsened prognosis in HF. SFRP2 is an independent biomarker for myocardial fibrosis. Further studies are needed to explore the potential therapeutic value of SFRP2 in myocardial fibrosis.

Metabolic changes and interaction of tumor cell, myeloid-derived suppressor cell and T cell in hypoxic microenvironment.

It is universally acknowledged that a large number of immune cells, as well as inflammatory factors, regulatory factors and metabolites, accumulate in the tumor microenvironment to jointly promote tumor escape, development and metastasis. Hypoxia is one of the characteristics in tumor microenvironment and is a common phenomenon in all solid tumors. In tumor hypoxia response, there is a key regulator called HIF-1a, which is a key transcriptional regulatory protein that regulates many critical genes. In this paper, the effects of hypoxia on glucose metabolism of tumor cells, myeloid-derived suppressor cells and T cells in tumor microenvironment were reviewed, and the interaction among the three was also described.

14-CpG-Based Signature Improves the Prognosis Prediction of Hepatocellular Carcinoma Patients.

BACKGROUND: Epigenetic dysregulation via alteration of DNA methylation often occurs during the development and progression of cancer, including hepatocellular carcinoma (HCC). In the past, many patterns of single-gene DNA methylation have been extensively explored in the context of HCC prognosis prediction. However, the combined model of a mixture of CpGs has rarely been evaluated. In the present study, we aimed to develop and validate a CpG-based signature model for HCC patient prognosis. METHODS: Data from methylation profiling of GSE73003, GSE37988, and GSE57958 from the Gene Expression Omnibus (GEO) database and 371 HCC patients from the Cancer Genome Atlas (TCGA) were downloaded. The 371 HCC patients were randomly divided into a development cohort (N = 263) and a validation cohort (N = 263) and a validation cohort (. RESULTS: Fourteen differential CpGs associated with OS were identified in HCC patients. The MSH, based on these 14 differential CpGs, could effectively divide HCC patients into two distinct subgroups with high risk or low risk of death (P < 0.0001) in the development cohort (26.35 vs 83.18 months, HR = 3.83, 95% CI: 2.56-5.90, P < 0.0001) in the development cohort (26.35 vs 83.18 months, HR = 3.83, 95% CI: 2.56-5.90, P < 0.0001) in the development cohort (26.35 vs 83.18 months, HR = 3.83, 95% CI: 2.56-5.90. CONCLUSION: The 14-CpG-based signature is significantly associated with OS and may be used as a novel prognostic biomarker for HCC patients.

A High-Salt Diet Disturbs the Development and Function of Natural Killer Cells in Mice.

A high-salt diet (HSD) is common worldwide and can lead to cardiovascular disease, chronic inflammation, and autoimmune diseases. Moreover, increasing evidence shows that HSD is closely related to a variety of immune diseases. Natural killer (NK) cells are important innate immune cells that directly kill their targets via degranulation and secretion of interferon gamma (IFN-γ). NK cells play a vital role in resisting viruses and preventing the malignant transformation of cells; however, whether HSD affects the development and function of NK cells has not yet been elucidated. Therefore, the purpose of the present study was to understand the effects of HSD on the development and function of NK cells, in addition to investigating the underlying molecular mechanism. Our results show that the number of NK cells in the spleen and lungs of HSD-fed mice was significantly reduced, which may be due to the inhibition of NK cell proliferation. Further, the development of NK cells in mice was evaluated, and it was found that HSD reduced the effective NK cell subset (CD27+CD11b-). Moreover, it was also found that the ability of NK cells to secrete CD107a and IFN-γ in HSD-fed mice was decreased following stimulation with RMA-S and YAC-1 tumor cells. Finally, the underlying molecular mechanism was evaluated, and it was found that HSD increased the production of reactive oxygen species (ROS) by NK cells, while the expression of CD122 was decreased, suggesting that HSD downregulates CD122 expression in NK cells via ROS signaling, thereby reducing the responsiveness to IL-15 and ultimately inhibiting NK cell function. The present research discovered a novel mechanism by which HSD inhibits the function of NK cells, providing an alternative avenue for the treatment of immune diseases caused by HSD.

Ahypoxia-related signature enhances the prediction of the prognosis in hepatocellular carcinoma patients and correlates with sorafenib treatment response.

Hepatocellular carcinoma (HCC) is one of the leading cancer death and is the primary malignancy of the liver. Tumor hypoxia is the stressor that is involved in tumorigenesis and significantly increased the aggressiveness of HCC. Here, we systematically analyzed the expression profiles and prognostic values of 84 hypoxia associated genes in HCC. mRNA expression of 84 hypoxia associated genes and clinical parameters of HCC patients were downloaded from TCGA, GSE14520, GSE109211 and ICGC. Consensus clustering analysis was performed for unsupervised classes on the basis of 84 hypoxia associated genes. Univariate and LASSO analysis were used to develop the risk signature. A risk signature was developed, including the expression of APEX1, ATR, CTSA, DNAJC5, ENO1, EPO, HMOX1, LDHA, NDRG1, and PER1, and found to be significantly related with OS and DFS of HCC patients. We stratified HCC patients into the high-risk group and low-risk group by means of the risk signature. Patients of high-risk group had shorter OS and DFS, while that of the low-risk group had longer OS and DFS. The risk signature showed better predictive efficiency than the TNM staging in predicting OS and DFS. Also, macrophage M0 cells, regulatory T cells, and neutrophils were found to be significantly enriched in patients of high-risk group. Next, we validated the discrimination and prognostic value of the risk signature in GSE14520 and the ICGC HCC cohort. Finally, significantly lower risk scores were found in sorafenib treatment responders of GSE109211 cohort, and the AUC for predicting sorafenib treatment response was 0.881. In conclusion, a risk signature developed with the expression of 10 hypoxia associated genes improved the prognosis prediction of HCC and correlated with sorafenib treatment response.

Prognostic value of Epstein-Barr virus DNA level for nasopharyngeal carcinoma: a meta-analysis of 8128 cases.

BACKGROUND: Plasma levels of Epstein-Barr virus (EBV) DNA have been employed to predict survival outcomes of patients with nasopharyngeal carcinoma (NPC). However, the prognostic value of subsequent EBV DNA levels (mid or post treatment) for NPC is needed to identify by a large cohort of patients. We performed a meta-analysis of studies including data from 8128 patients to evaluate the prognostic value of EBV DNA in NPC patients. METHODS: We searched PubMed, Web of Science, and the Cochrane library for prospective and retrospective studies. Hazard ratios (HRs) and confidence intervals (CIs) were extracted from the studies or calculated and pooled to assess the association between EBV DNA levels pre-treatment (pre-DNA), mid-treatment (mid-DNA), and post-treatment (post-DNA) on clinical outcomes. RESULTS: A total of 22 studies with 8128 patients was included for analysis. Pre-DNA levels predicted overall survival, progression-free survival, distant metastasis-free survival, and local-regional failure survival with HRs (95% CIs) of 2.70 (2.06, 3.54), 2.70 (2.12, 3.44), 3.49 (2.35, 5.17), and 2.00 (1.45, 2.76), respectively, and the corresponding HRs for post-DNA levels were 4.86 (3.30, 7.17), 6.29 (3.41, 11.60), 5.68 (2.71,11.93), respectively. Mid-DNA levels predicted overall survival and progression-free survival with an HR (95% CI) of 3.02 (1.54, 5.29) and 3.15 (2.05, 4.83). Subgroup analysis showed that the HR of post-DNA wasn't influenced by different detection time of post-DNA (P = 0.22, I2 = 33.2%). CONCLUSION: The EBV DNA levels have a significant prognostic impact in patients with NPC. The effect of post-treatment EBV DNA level dominated that of pre-DNA and mid-DNA levels.

Draft genome sequence of an OXA-23, OXA-66, ADC-25 and TEM-1D co-producing Acinetobacter baumannii ST195 isolated from a patient with neonatal pneumonia in China.

OBJECTIVES: The rapid spread of multidrug-resistant (MDR) Acinetobacter baumannii poses a substantial threat for morbidity and mortality worldwide. In particular, carbapenem-resistant A. baumannii has caused a severe challenge to human health. Here we reported the draft genome sequence of A. baumannii S131434, an OXA-23, OXA-66, ADC-25 and TEM-1D co-producing strain recovered from a patient with neonatal pneumonia in China and belonging to the globally disseminated sequence type 195 (ST195) of clonal complex 92 (CC92). METHODS: Genomic DNA was sequenced using an Illumina HiSeq platform and the reads were de novo assembled into contigs using CLC Genomics Workbench. The assembled contigs were annotated and bioinformatics analysis was performed. RESULTS: The genome comprised a circular chromosome of 3898344bp. The presence of the blaOXA-23, blaOXA-66, blaADC-25 and blaTEM-1D genes was detected. In addition, genes conferring resistance to aminoglycosides, macrolides and tetracycline were also identified. Antimicrobial susceptibility testing revealed that the isolate was resistant to all of the tested antibiotics except for polymyxin B, piperacillin/sulbactam and trimethoprim/sulfamethoxazole. CONCLUSION: To our knowledge, this is the first report of a clinical A. baumannii ST195 (CC92) isolate producing OXA-23, OXA-66, ADC-25 and TEM-1D in southern China. This draft genome will facilitate further our understanding of the antimicrobial resistance and pathogenic mechanisms in this strain and provides valuable information regarding the colonisation and adaptation of MDR pathogens.

In vitro Antibacterial Activity of Isopropoxy Benzene Guanidine Against Multidrug-Resistant Enterococci.

BACKGROUND: Bacterial infections cause a serious public health crisis due to the emergence of resistance towards multiple conventional antibacterial drugs. In particular, multidrug-resistant (MDR) Enterococcus faecium which belongs to "ESKAPE" organisms is causing significant problems worldwide. Hence, there is an urgent need to find alternative therapies. Recently, substituted benzene guanidine compounds have been used as lead structures to discover new promising drugs in both synthetic and medicinal chemistry. PURPOSE: Here we investigated the antimicrobial activity of a new substituted benzene guanidine analog, isopropoxy benzene guanidine, against Enterococci. MATERIAL AND METHODS: The isopropoxy benzene guanidine was synthesized by Guangzhou Insighter Biotechnology Co., Ltd and tested on both reference bacterial strain and 32 clinical MDR Enterococci strains. The in vitro antibacterial activity was evaluated by microdilution method and kill kinetic assays. The potential antibacterial mechanism was measured by fluorescence spectrometry using fluorescent membrane potential probe 3, 3-diethyloxacarbocyanine iodide (DiOC2 (3)). RESULTS: Isopropoxy benzene guanidine exhibited potent bactericidal activity against both reference strain and MDR Enterococci isolates. The minimum inhibitory concentration (MIC) range for isopropoxy benzene guanidine was 1-4 µg/mL. Minimum bactericidal concentration (MBC) was about 2-8-fold of its MIC values. Time-kill studies showed that isopropoxy benzene guanidine provided superior bactericidal effect against reference and MDR strains within 12 hrs at 2×MIC. Furthermore, isopropoxy benzene guanidine could cause a large reduction in the magnitude of the generated membrane potential compared to that of the untreated cells. CONCLUSION: The present study highlights the potent bactericidal activity of isopropoxy benzene guanidine on Enterococci by disrupting the cell membrane potential. These findings demonstrate that isopropoxy benzene guanidine may be a good chemical lead for further medicinal chemistry and pharmaceutical development and could be used as a therapeutic agent for infectious diseases caused by MDR Enterococci.

Gamma-Glutamyltransferase and Risk of Acute Coronary Syndrome in Young Chinese Patients: A Case-Control Study.

BACKGROUND: Serum gamma-glutamyltransferase (GGT) is a biomarker of hepatic disease. Recent studies have shown that GGT may also associate with the risk of coronary artery disease. However, the underlying mechanisms of this association are still unclear. METHODS: This study included 216 young patients with acute coronary syndrome (aged ≤55years) and 227 age-matched controls with normal findings by coronary angiography or coronary computed tomography angiography. We use standard colorimetric techniques and sandwich enzyme-linked immunosorbent assay to measure the levels of GGT and oxidized low-density lipoprotein (ox-LDL), respectively. Traditional risk factors of coronary artery disease, including smoking, diabetes mellitus, hypertension, dyslipidemia, and obesity/overweight, were evaluated according to the current guidelines. RESULTS: The levels of GGT were significantly correlated with body mass index and levels of triglyceride, fasting plasma glucose, aspartate aminotransferase, and ox-LDL (all P < 0.05). Multivariate logistic regression analysis showed that GGT was significantly associated with the risk of acute coronary syndrome in young Chinese patients (OR = 1.53, 95% CI = 1.09-2.15) after adjusting for traditional risk factors, including sex, age, quantity of smoking, hypertension, diabetes, body mass index, dyslipidemia, and high-sensitivity C-reactive protein. However, this association was significantly attenuated (OR = 1.20, 95% CI = 0.91-1.58) after further adjusting for the levels of ox-LDL. CONCLUSIONS: GGT was associated with the risk of ACS in relatively young patients. The link between GGT and the risk of ACS may be dependent on ox-LDL levels, indicating that the prooxidant action is an important pathway for GGT in the development of cardiovascular disease.

A potentially functional variant of ARID1B interacts with physical activity in association with risk of hepatocellular carcinoma.

The tumor suppressor role of AT-rich interactive domain containing protein 1B (ARID1B) has drawn much attention in area of cancer etiology. However, it had remained unknown whether or not genetic variants of ARID1B involved in development of hepatocellular carcinoma (HCC). In this study, three putatively functional variants in ARID1B (rs73013281C>T, rs167007A>G, and rs9397984C>T) were selected using bioinformatics tools, and a case-control study of 611 cases and 614 controls was conducted to investigate genetic associations with HCC risk in a Southern Chinese population. Two-dimensional gene-environment interactions were also explored using both multiplicative and additive scales. A dominant effect of the rs73013281 was found for HCC risk, with an adjusted odds ratio (OR) of 1.70 [95% confidence interval (CI) = 1.03-2.80] for the CT/TT genotypes compared to the CC genotype. In stratified analysis, the detrimental effect of the T allele on elevated HCC risk was attenuated by physical activity, with an adjusted OR of 2.75 (95% CI = 1.39-5.41) among inactive individuals against that of 0.89 (95% CI = 0.42-1.91) in those who exercised regularly. Expectably, the rs73013281 showed both multiplicative and additive interactions with physical activity (P = 0.037 and 0.006, respectively). In conclusion, these results highlighted the significant genetic contribution of the ARID1B variant, rs73013281, to susceptibility for HCC, especially in interaction with physical activity.

The Role of NADPH Oxidase in the Inhibition of Trichophyton rubrum by 420-nm Intense Pulsed Light.

Objectives: To evaluate the effect of intense pulsed light (IPL) on Trichophyton rubrum and investigate its mechanism of action. Methods: The viability of fungi treated with IPL alone and with IPL combined with an NADPH oxidase inhibitor (DPI) pretreatment was determined by MTT assays. The reactive oxygen species (ROS) were quantified with a DCFH-DA fluorescent probe. Malondialdehyde (MDA) content and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined by commercial kits. The transcription of the Nox gene was quantified using quantitative real-time PCR (qRT-PCR) analysis, and micromorphology was observed using scanning electron microscopy (SEM). In addition, fungal keratinase activity was detected by measuring dye release from keratin azure. Results: The growth declined with statistical significance after 6 h of treatment (P < 0.001). The ROS and MDA content increased after IPL treatment, whereas the SOD and GSH-Px activity decreased. Nox gene expression was upregulated, and the micromorphology was damaged. Keratinase activity decreased. Fungi that received DPI pretreatment exhibited contrasting outcomes. Conclusion: We found that 420-nm IPL significantly inhibited the growth and pathogenicity of T. rubrum in vitro. A suggested mechanism involves Nox as a factor that mediates 420-nm IPL-induced oxidative damage of T. rubrum.

Effects of interactions between environmental factors and KIF1B genetic variants on the risk of hepatocellular carcinoma in a Chinese cohort.

AIM: To examine the effect of the potential interaction between KIF1B variants (rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma (HCC) in a high-risk region in China. METHODS: Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination. Two single nucleotide polymorphisms (SNPs) of KIF1B (rs17401966 and rs3748578) were chosen for the current study. All subjects were genotyped using a TaqMan real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions. RESULTS: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus (HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio (OR) = 12.02; 95% confidence interval (95%CI): 6.02-24.00]. No significant association was found between the KIF1B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption (P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC (OR = 2.36; 95%CI: 1.49-3.74). CONCLUSION: The gene-environment interaction between the KIF1B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.

[Association of C677T gene polymorphisms of methylenetetrahydrofolate reductase and plasma homocysteine level with hyperlipidemia].

OBJECTIVE: To study the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and plasma homocysteine (Hcy) levels with hyperlipidemia. METHODS: Blood samples were collected from 1591 adults for detecting MTHFR gene C677T polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), plasma Hcy levels with enzymatic cycling method, and blood lipid levels as well. The patients were divided according to the lipid levels into hyperlipidemia group (n=694) and healthy control group (n=897) and the differences in MTHFR gene C677T polymorphisms and plasma Hcy levels were compared. RESULTS: The hyperlipidemia group and healthy control group showed no significant differences in CC, CT, or TT genotype frequencies or C and T allele frequencies of MTHFR C677T gene, and had comparable plasma Hcy levels (P>0.05). Patients with 3 different MTHFR C677T genotypes had significant differences in plasma Hcy levels (P<0.01) but not in blood lipid levels (P>0.05). Pairwise comparison indicated a significantly higher plasma Hcy level in TT genotype than in CC and CT genotypes (P<0.01), and the latter two genotypes showed no significant difference (P>0.05). CONCLUSION: MTHFR C677T polymorphisms and plasma Hcy levels are closely related but neither of them is associated with hyperlipidemia. The TT genotype is associated with a significantly higher plasma Hcy level than CC and CT genotypes.