TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis.

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Hydrophobicity Tuning of Cationic Polyaspartamide Derivatives for Enhanced Antisense Oligonucleotide Delivery.

Various cationic polymers are used to deliver polyplex-mediated antisense oligonucleotides (ASOs). However, few studies have investigated the structural determinants of polyplex functionalities in polymers. This study focused on the polymer hydrophobicity. A series of amphiphilic polyaspartamide derivatives possessing various hydrophobic (R) moieties together with cationic diethylenetriamine (DET) moieties in the side chain (PAsp(DET/R)s) were synthesized to optimize the R moieties (or hydrophobicity) for locked nucleic acid (LNA) gapmer ASO delivery. The gene knockdown efficiencies of PAsp(DET/R) polyplexes were plotted against a hydrophobicity parameter, logD7.3, of PAsp(DET/R), revealing that the gene knockdown efficiency was substantially improved by PAsp(DET/R) with logD7.3 higher than -2.4. This was explained by the increased polyplex stability and improved cellular uptake of ASO payloads. After intratracheal administration, the polyplex samples with a higher logD7.3 than -2.4 induced a significantly higher gene knockdown in the lung tissue compared with counterparts with lower hydrophobicity and naked ASO. These results demonstrate that the hydrophobicity of PAsp(DET/R) is crucial for efficient ASO delivery in vitro and in vivo.

In-situ construction of fluorescent probes for hydrogen peroxide detection in mitochondria and lysosomes with on-demand modular assembling and double turn-on features.

Due to the diverse H2O2 distribution in organelles, fluorescent probes were usually required to be prepared separately, which limited the convenience and practicability. Herein, we reported a flexible strategy to in-situ construct H2O2 fluorescent probes in different organelles. A tetrazine fused probe TP was developed with rapid click reaction capacity and sensitive H2O2 response. When treated with H2O2, the turn-on fluorescence was effectively quenched by the tetrazine part. Only after click reaction with dienophiles, the fluorescence resumed. In application, cells were firstly treated with triphenylphosphorus tagged norbornene (TPP-NB) to label mitochondria, which was followed by the introduction of probe TP to trigger click reaction. The in-situ constructed probe P1 served as a local H2O2 sensor. In a similar way, probe P2 was in-situ constructed in lysosomes via probe TP and morpholine tagged norbornene (MP-NB). With this on-demand modular assembling and double turn-on features, our strategy to construct fluorescent probes presented high flexibility and anti-interference performance, which was expected to inspired more applications in biological studies.

α-Cyperone ameliorates depression in mammary gland hyperplasia and chronic unpredictable mild stress rat by regulating hormone, inflammation, and oxidative stress.

BACKGROUND: Hyperplasia of mammary gland (HMG) is caused by endocrine disorders, and patients are prone to anxiety and depression. α-Cyperone has a variety of pharmacological activities including antidepressant. The purpose of this study was to explore the effect and its possible mechanism of α-Cyperone on HMG-associated depression rats. METHODS: The depression model was constructed using chronic unpredictable mild stress (CUMS), while the HMG model was induced by estrogen, with or without α-Cyperone intervention. The effect of α-Cyperone on the depression-like phenotype of model rats was measured by sucrose preference test (SPT), forced swim test (FST), and open field test (OFT). Dendritic spines density in ventral medial prefrontal cortex (vmPFC) neurons was evaluated by Golgi staining. The second pair of nipple height, diameter, organ index, and oxidative stress-related factors were analyzed. Serum sex hormone concentration, histopathological changes, inflammatory factor expression, and p65 were evaluated by enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) staining, real-time quantitative PCR and western blot, respectively. RESULTS: The sucrose preference rate, dendritic spine density decreased, and immobility time increased in CUMS rats; α-Cyperone reversed the effect of CUMS on depression-like behavior and dendritic spine density in rats. α-Cyperone reduced nipple height and diameter, uterine index, estradiol concentration, increased ovary, thymus, spleen index, progesterone, and testosterone concentration, relieved pathological damage, oxidative stress, depression-like behavior, and inflammatory reaction in HMG combine CUMS rats. In addition, α-Cyperone inhibited the phosphorylation of p65 in HMG and CUMS rats. CONCLUSIONS: α-Cyperone has an effective therapeutic effect on HMG combined with CUMS rats.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

Bacterial cellulose as an oleaginous yeast cell carrier for soybean oil refinery effluent treatment and pyrolysis oil production.

Bacterial cellulose produced from soybean oil refinery effluent is a good immobilization carrier because of the large pores in its fiber network, its high water-holding capacity, and its good biocompatibility. In this study, it was applied to immobilization of oleaginous yeasts for treating soybean oil refinery effluent. The immobilization percentage reached 50%, and the removal of chemical oxygen demand and oil content reached 92.1% and 93.1%, respectively, during dynamic immobilization using a mass percentage of bacterial cellulose of 30% and an immobilization time of 24 h, which were significantly higher than those of free oleaginous yeasts or yeasts immobilized by bacterial cellulose from rich medium. The immobilized oleaginous yeasts facilitated the recovery of the yeasts and effectively treated three batches of soybean oil refinery effluent. The immobilized oleaginous yeasts recovered after soybean oil refinery effluent treatment were pyrolyzed to produce bio-oil, which contributed to more alkanes and a higher calorific value of bio-oil in the pyrolysis products as compared to those of free oleaginous yeasts. As bacterial cellulose used as an oleaginous yeast cell carrier is produced from soybean oil refinery effluent, no waste of immobilization materials is involved and an efficient waste-into-oil bioprocess is developed.

Metabolic reprogramming-associated genes predict overall survival for rectal cancer.

Metabolic reprogramming has become a hot topic recently in the regulation of tumour biology. Although hundreds of altered metabolic genes have been reported to be associated with tumour development and progression, the important prognostic role of these metabolic genes remains unknown. We downloaded messenger RNA expression profiles and clinicopathological data from The Cancer Genome Atlas and the Gene Expression Omnibus database to uncover the prognostic role of these metabolic genes. Univariate Cox regression analysis and lasso Cox regression model were utilized in this study to screen prognostic associated metabolic genes. Patients with high-risk demonstrated significantly poorer survival outcomes than patients with low-risk in the TCGA database. Also, patients with high-risk still showed significantly poorer survival outcomes than patients with low-risk in the GEO database. What is more, gene set enrichment analyses were performed in this study to uncover significantly enriched GO terms and pathways in order to help identify potential underlying mechanisms. Our study identified some survival-related metabolic genes for rectal cancer prognosis prediction. These genes might play essential roles in the regulation of metabolic microenvironment and in providing significant potential biomarkers in metabolic treatment.

Maresin1 Promotes M2 Macrophage Polarization Through Peroxisome Proliferator-Activated Receptor-γ Activation to Expedite Resolution of Acute Lung Injury.

BACKGROUND: Acute lung injury (ALI), manifested by progressive hypoxemia and respiratory distress, is associated with high morbidity and mortality, which lacks the effective therapies in clinics. Our previous studies demonstrated that maresin1 (MaR1), a specialized proresolving mediator, could effectively mitigate the inflammation of lipopolysaccharide (LPS)-induced ALI. However, whether MaR1 impacts the macrophage polarization to alleviate ALI remains unclear. Our study explored the effects and underlying mechanisms of MaR1 on the macrophage phenotypes in ALI. MATERIAL AND METHODS: Male BALB/c mice were subjected to endotracheal instillation of LPS to induce ALI and then intravenously injected with MaR1 or normal saline. Intraperitoneal administration of peroxisome proliferator-activated receptor-γ (PPAR-γ) inhibitor GW9662 was given 30 mins before MaR1. We measured the pathohistologic changes, pulmonary edema, inflammatory cytokines, and the flow cytometry of macrophage phenotypes. RESULTS: Our results illustrated that MaR1 ameliorated lung injury and increased monocyte or macrophage recruitment and the release of anti-inflammatory cytokines. The flow cytometry showed that MaR1 promoted polarization of CD11c-CD206+ (M2) macrophages and inhibited polarization of CD11c+CD206- (M1) macrophages. Besides, the western blotting revealed that MaR1 increased the expression of PPAR-γ. The pretreatment with PPAR-γ antagonist GW9662 could significantly suppress the polarization of M2 macrophages and antagonize the protective effects of MaR1 on LPS-stimulated ALI. CONCLUSIONS: MaR1 was able to promote M2 macrophage polarization by reversing LPS-mediated PPAR-γ inhibition, thereby expediting the recovery of LPS-stimulated ALI.

Systemic In Silico Screening in Drug Discovery for Coronavirus Disease (COVID-19) with an Online Interactive Web Server.

The emergence of the new coronavirus (nCoV-19) has impacted human health on a global scale, while the interaction between the virus and the host is the foundation of the disease. The viral genome codes a cluster of proteins, each with a unique function in the event of host invasion or viral development. Under the current adverse situation, we employ virtual screening tools in searching for drugs and natural products which have been already deposited in DrugBank in an attempt to accelerate the drug discovery process. This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor. Additionally, we have built an interactive online platform (https://shennongproject.ai/) for browsing these results with the visual display of a small molecule docked on its potential target protein, without installing any specialized structural software. With continuous maintenance and incorporation of data from laboratory work, it may serve not only as the assessment tool for the new drug discovery but also an educational web site for the public.

Hangzhou criteria as downstaging criteria in hepatocellular carcinoma before liver transplantation: A multicenter study from China.

BACKGROUND: The downstaging of hepatocellular carcinoma (HCC) has been confirmed to benefit liver transplantation (LT) patients whose tumors are beyond the transplantation criteria. Milan criteria (MC), a tumor size and number-based assessment, is currently used as the endpoint in these patients. However, many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy. Hence, this study aimed to explore the feasibility of Hangzhou criteria (HC), which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number, as an endpoint of downstaging. METHODS: We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy (LRT) as downstaging/bridge treatment prior to LT in three centers of China. RESULTS: Recipients were divided into four groups: failed downstaging to the HC (group A, n = 46), successful downstaging to the HC (group B, n = 30), remained within the HC all the time (group C, n = 113), and tumor progressed (group D, n = 17). The 3-year HCC recurrence probabilities of groups B and C were not significantly different (10.3% vs. 11.6%, P = 0.87). The HCC recurrent rate was significantly higher in group A (52.3%) compared with that in group B/C (P < 0.05). Seven patients (7/76, 9.2%) whose tumor exceeded the the HC were successfully downstaged to the MC, and 39.5% (30/76) to the the HC. In group B, 23 patients remained beyond the MC and their survivals were as well as those of patients within the MC. CONCLUSIONS: Compared to the MC, HC downstaging criteria can give more HCC patients access to LT and furthermore, the outcome of these patients is the same as those matching MC downstaging criteria. Hangzhou downstaging criteria therefore is applicable in clinical practice.

Fluorimetric Detection of Candida albicans Using Cornstalk N-Carbon Quantum Dots Modified with Amphotericin B.

Due to the advanced fluorescence property of N-carbon quantum dots (N-CQDs), a new method to detect pathogenic fungi by newly synthesized cornstalk N-CQDs modified with water-soluble amphotericin B (N-CQDs@AmpB) was developed. Specifically, N-CQDs with blue fluorescence were initially synthesized according to a previous report and modified with amphotericin B on their surfaces. Subsequently, the as-prepared N-CQDs@AmpB was used to detect Candida albicans, exhibiting a linear range of 2.60 × 105 to 1.99 × 108 cfu/mL and a detection limit of 1124 cfu/mL. Compared with other common methods, the method largely shortened the detection time and enabled the process to be performed with minimal interference from complex samples such as beef sausage. The high cost of water-soluble amphotericin B may hamper the large-scale application of the new detection method using N-CQDs@AmpB. Thus, alcohol-soluble amphotericin B was used in subsequent experiments, confirming its potential to broaden avenues for the detection of fungi.

Additive interaction of snoring and body mass index on the prevalence of metabolic syndrome among Chinese coal mine employees: a cross-sectional study.

BACKGROUND: Although snoring has been previously reported to be associated with metabolic syndrome (MetS), its interaction with body mass index(BMI) on MetS remains unclear. We aimed to examine the individual effects and possible interaction between snoring and BMI on MetS. METHODS: From July 2013 to December 2013, 3794 employees of coal mining enterprises aged 18 to 65 were recruited from Shanxi province of China. The individual effects were assessed by multivariable logistic regression model. Additive interaction was evaluated by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index(S). RESULTS: We found that, after adjusting for potential confounders, odds ratio (OR) and 95% CI for MetS was 1.30 (1.09, 1.56) in occasional snorers and 1.50 (1.24, 1.82) in habitual snorers compared with non-snorers. BMI ≥ 24 was related to high risk of MetS (OR, 3.27; 95% CI, 2.93-3.63). Significant additive interaction between snoring and BMI on MetS was detected. The estimates and 95% CI of the RERI, AP and S were 1.89 (0.67, 3.24), 0.23 (0.08, 0.38), and 1.37 (1.11, 1.75), respectively. However, stratified by workplace, the additive interaction was only significant among underground front-line and ground workers. CONCLUSIONS: Both Snoring and BMI were related to high risk of Mets. Moreover, there are additive interaction between snoring and BMI. Snorers who worked underground front-line and ground are more susceptible to the negative impact of being overweight on MetS.

Trichosporon fermentans biomass flocculation from soybean oil refinery wastewater using bioflocculant produced from Paecilomyces sp. M2-1.

The soybean oil refinery (SOR) wastewater contains a high concentration of chemical oxygen demand (COD) and lipid, so the direct emissions of SOR wastewater will result in environmental pollution and waste of resources. Oleaginous yeast Trichosporon fermentans can consume organic materials in SOR wastewater to synthesize microbial oil, which achieves the purpose of SOR wastewater resource utilization. The effective harvesting technology of oleaginous yeasts can improve the utilization efficiency. In this study, Paecilomyces sp. M2-1 with high flocculating activity was isolated. The flocculants produced by M2-1 (MBF2-1) include 75% (w/w) polysaccharides, rely on cations, and display the flocculation percentage of above 77% in the range of pH 2-11. Especially under alkaline conditions, the flocculation percentage can be kept above 97%. The results of scanning electron microscope observation and zeta potential measurements suggested that the bridging, net trapping, and sweeping were the main flocculation mechanism of MBF2-1. MBF2-1 could flocculate T. fermentans that was used to reduce the organic matter in SOR wastewater and to produce microbial oil. Under the optimum conditions, the flocculation percentage of MBF2-1 against T. fermentans from SOR wastewater can reach 95%. Fatty acid content percent in microbial oil from T. fermentans was not almost affected by flocculation of MBF2-1. Moreover, MBF2-1 can further remove 55% and 53% of COD and oil content in the fermented SOR wastewater, respectively. The properties and high flocculating percentage displayed by MBF2-1 indicated its potential application prospect in oleaginous yeast harvest and food industry wastewater treatment.

Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells.

Proper neural commitment is essential for ensuring the appropriate development of the human brain and for preventing neurodevelopmental diseases such as autism spectrum disorders, schizophrenia, and intellectual disorders. However, the molecular mechanisms underlying the neural commitment in humans remain elusive. Here, we report the establishment of a neural differentiation system based on human embryonic stem cells (hESCs) and on comprehensive RNA sequencing analysis of transcriptome dynamics during early hESC differentiation. Using weighted gene co-expression network analysis, we reveal that the hESC neurodevelopmental trajectory has five stages: pluripotency (day 0); differentiation initiation (days 2, 4, and 6); neural commitment (days 8-10); neural progenitor cell proliferation (days 12, 14, and 16); and neuronal differentiation (days 18, 20, and 22). These stages were characterized by unique module genes, which may recapitulate the early human cortical development. Moreover, a comparison of our RNA-sequencing data with several other transcriptome profiling datasets from mice and humans indicated that Module 3 associated with the day 8-10 stage is a critical window of fate switch from the pluripotency to the neural lineage. Interestingly, at this stage, no key extrinsic signals were activated. In contrast, using CRISPR/Cas9-mediated gene knockouts, we also found that intrinsic hub transcription factors, including the schizophrenia-associated SIX3 gene and septo-optic dysplasia-related HESX1 gene, are required to program hESC neural determination. Our results improve the understanding of the mechanism of neural commitment in the human brain and may help elucidate the etiology of human mental disorders and advance therapies for managing these conditions.

Single-cell-level spatial gene expression in the embryonic neural differentiation niche.

With the rapidly increasing availability of high-throughput in situ hybridization images, how to effectively analyze these images at high resolution for global patterns and testable hypotheses has become an urgent challenge. Here we developed a semi-automated image analysis pipeline to analyze in situ hybridization images of E14.5 mouse embryos at single-cell resolution for more than 1600 telencephalon-expressed genes from the Eurexpress database. Using this pipeline, we derived the spatial gene expression profiles at single-cell resolution across the cortical layers to gain insight into the key processes occurring during cerebral cortex development. These profiles displayed high spatial modularity in gene expression, precisely recapitulated known differentiation zones, and uncovered additional unknown transition zones or cellular states. In particular, they revealed a distinctive spatial transition phase dedicated to chromatin remodeling events during neural differentiation, which can be validated by genomic clustering patterns, epigenetic modifications switches, and network modules. Our analysis further revealed a role of mitotic checkpoints during spatial gene expression state transition. As a novel approach to analyzing at the single-cell level the spatial modularity, dynamic trajectory, and transient states of gene expression during embryonic neural differentiation and to inferring regulatory events, our approach will be useful and applicable in many different systems for understanding the dynamic differentiation processes in vivo and at high resolution.

Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2.

Human carboxylesterases (hCEs) are key enzymes from the serine hydrolase superfamily. Among all identified hCEs, human carboxylesterase 2 (hCE2) plays crucial roles in the metabolic activation of ester drugs including irinotecan and flutamide. Selective and potent hCE2 inhibitors could be used to alleviate the toxicity induced by hCE2-substrate drugs. In this study, more than fifty flavonoids were collected to assay their inhibitory effects against hCE2 using a fluorescence-based method. The results demonstrated that C3 and C6 hydroxy groups were essential for hCE2 inhibition, while O-glycosylation or C-glycosylation would lead to the loss of hCE2 inhibition. Among all tested flavonoids, 5,6-dihydroxyflavone displayed the most potent inhibitory effect against hCE2 with the IC50 value of 3.50 µM. The inhibition mechanism of 5,6-dihydroxyflavone was further investigated by both experimental and docking simulations. All these findings are very helpful for the medicinal chemists to design and develop more potent and highly selective flavonoid-type hCE2 inhibitors.

Intestinal T-cell and NK/T-cell lymphomas: A clinicopathological study of 27 Chinese patients.

BACKGROUND: Intestinal T-cell and NK/T- cell lymphomas are rare and aggressive. The diagnosis is quite difficult, especial in biopsy specimens. This study investigates the clinicopathological features of intestinal T-cell and NK/T-cell lymphomas to aid their differential diagnosis. METHODS: Clinical data of 27 cases were collected. Including extranodal NK/T-cell lymphoma, nasal type (ENKTCL-N), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), anaplastic large-cell lymphoma, ALK+ (ALCL, ALK+) and angioimmunoblastic T-cell lymphoma (AITL). The histologic features, immunohistochemical findings, T-cell receptor gene rearrangement results, and follow-up data were analyzed, with review of literature. RESULTS: The age of the patients (N = 27) was 15-85 years (mean, 47.5 years), and male:female ratio, 3.5:1. Abdominal pain and B symptoms were the most common symptoms. Although 85.2% of the patients were in clinical stage I-II, 59.3% died within 1 year. MEITL showed certain distinctive clinic opathological features from ENKTCL-N. Compared to lesions at other sites, there were no differences in the morphological features, immunophenotype and TCR gene rearrangement of intestinal ENKTCL-N, PTCL, NOS, ALCL, ALK+ and AITL. CONCLUSION: Intestinal T-cell and NK/T-cell lymphomas are a heterogeneous group of lymphomas. They could be classified to 5 histological subtypes in our study. ENKTCL-N and MEITL formed the majority of the tumor types. Each subtype has distinctive pathological features, but most of them have diamal prognosis.

Prevalence of dyslipidaemia and risk factors in Chinese coal miners: a cross-sectional survey study.

BACKGROUND: Although coal miners are susceptible to dyslipidaemia owing to their highly risky and stressful working environment as well as unhealthy lifestyle, very few studies have focused on this issue thus far. Therefore, this study investigated the current epidemiological characteristics of dyslipidaemia among Chinese coal miners. METHODS: Demographic, anthropometric, and biochemical data were gathered from 4341 coal miners in China. Dyslipidaemia was diagnosed based on the serum lipid levels. Univariate and multivariate logistic regression analyses were used to assess the related risk factors for dyslipidaemia. RESULTS: The average concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 5.01 ± 0.93 mmol/L, 1.90 ± 1.72 mmol/L, 1.21 ± 0.35 mmol/L, and 3.15 ± 0.80 mmol/L, respectively. Additionally, 38.08% of participants had a high TC level, 25.84% had a low HDL-C level, 35.08% had a high LDL-C level, and 40.46% had a high TG level. The overall prevalence of dyslipidaemia was 68.28% (95% CI: 66.90-69.66%). Factors associated with dyslipidaemia were age, sex, marital status, monthly family income, type of work, length of service, smoking status, smoking index, drinking status, alcohol consumption per day, elevated fasting glucose, hypertension, obesity and abdominal obesity. CONCLUSIONS: Our study's results indicated a very high prevalence of dyslipidaemia among Chinese coal miners and identified various risk factors for dyslipidaemia.

Relationship Between Physical Activity Patterns and Metabolic Syndrome Among Male Coal Miners of Shanxi Province in China.

OBJECTIVE: This study aimed to investigate the relationship between metabolic syndrome (MetS) and physical activity (PA) in different domains among male coal miners of Shanxi Province in China. METHOD: The study was conducted from July 2013 to December 2013. A two-stage stratified cluster sampling method was used. Data regarding the general information of participants were collected by well-trained interviewers. MetS was defined according to IDF criteria. Self-reported PA was obtained with the IPAQ and categorized into three tertiles of intensity levels across occupation, transportation, household, and leisure-time domains. Univariate and multiple logistic regression analysis were applied to compute the odds ratios and their 95% confidence interval (CI). RESULTS: A total of 3076 males aged 18-65 years old were recruited in this cross-sectional study. The prevalence of MetS was 40.5% in the study subjects. The percentages of vigorous-intensity PA in MetS and non-MetS groups were 70.07% and 62.92%, respectively. Participants spent most of their time on occupation (2034 MET-min/w) and transportation (693MET-min/w) domains. Higher-intensity levels in occupation domains were significantly associated with lower risk of MetS (OR: 0.759, 95% CI: 0.633-0.911; OR: 0.627, 95% CI: 0.516-0.762). CONCLUSIONS: Across four types of workers, the relationships between PA domains and MetS were different. For underground and underground auxiliary workers, the negative relationship was found between occupation PA and MetS. For office workers, the negative relationship was found between household PA and MetS. For ground workers, only leisure-time PA had positively related to MetS.

The risk of new-onset cancer associated with HFE C282Y and H63D mutations: evidence from 87,028 participants.

To investigate the association between mutation of HFE (the principal pathogenic gene in hereditary haemochromatosis) and risk of cancer, we conducted a meta-analysis of all available case-control or cohort studies relating to two missense mutations, C282Y and H63D mutations. Eligible studies were identified by searching databases including PubMed, Embase and the ISI Web of Knowledge. Overall and subgroup analyses were performed and odds ratios (ORs) combined with 95% confidence intervals (CIs) were applied to evaluate the association between C282Y mutation, H63D mutation and cancer risk. Sensitivity and cumulative analyses were used to evaluate the stability of the results. A total of 36 eligible studies were included, comprising 13,680 cases and 73,348 controls. C282Y was significantly associated with elevated cancer risk in a recessive genetic model (OR: 1.991, 95% CI: 1.448-2.737). On subgroup analysis stratified by cancer type, statistically significantly increased cancer risks were found for breast cancer, colorectal cancer and hepatocellular carcinoma in a recessive model. When stratified by territory, a significantly increased risk of cancer was found in Oceanic populations in a recessive model and in Asian populations in an allele model and dominant model. H63D mutation did not significantly increase overall cancer risk in any genetic model. However, when, stratified by territory, an increased cancer risk was found in the Asian population in an allele and dominant. C282Y but not H63D mutation was related to elevated cancer risk. Further large-scale studies considering gene-environment interactions and functional research should be conducted to further investigate this association.