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As a common air pollutant, formaldehyde is widely present in nature, industrial production and consumer products. Endogenous formaldehyde is mainly produced through the oxidative deamination of methylamine catalysed by semicarbazide‐sensitive amine oxidase (SSAO) and is ubiquitous in human body fluids, tissues and cells. Vascular endothelial cells and smooth muscle cells are rich in this formaldehyde‐producing enzyme and are easily damaged owing to consequent cytotoxicity. Consistent with this, increasing evidence suggests that the cardiovascular system and stages of heart development are also susceptible to the harmful effects of formaldehyde. Exposure to formaldehyde from different sources can induce heart disease such as arrhythmia, myocardial infarction (MI), heart failure (HF) and atherosclerosis (AS). In particular, long‐term exposure to high concentrations of formaldehyde in pregnant women is more likely to affect embryonic development and cause heart malformations than long‐term exposure to low concentrations of formaldehyde. Specifically, the ability of mouse embryos to effect formaldehyde clearance is far lower than that of the rat embryos, more readily allowing its accumulation. Formaldehyde may also exert toxic effects on heart development by inducing oxidative stress and cardiomyocyte apoptosis. This review focuses on the current progress in understanding the influence and underlying mechanisms of formaldehyde on cardiovascular disease and heart development.

We investigated the association between respiratory health and particulate matter (PM) air pollution in elderly type 2 diabetes mellitus (T2DM) pre-, during, and post-the Chinese Lunar New Year (CLNY) holiday in Shanghai, China.We conducted repeated measurements of lung function and inflammation biomarker in a cohort consisted of 60 participants with T2DM.Decreased PM2.5 exposure had an effect on respiratory health by increasing in forced expiratory flow in 1 second (FEV1) and forced vital capacity (FVC). Positive associations between PM exposure and exhaled nitric oxide (eNO) were observed.Our observations indicated that PM air pollution exposure would exert adverse effect on respiratory health in elderly T2DM population.

Glucocorticoids (GCs) are widely prescribed as adjuvant therapy for breast cancer patients. Unlike other steroid hormone receptors, the GC receptor is not considered an oncogene. Research in the past few years has revealed the complexity of GC-mediated signaling, but it remains puzzling whether GCs promote or inhibit tumor progression in different cancer types. Here we evaluated the potential of using a synthetic GC, dexamethasone (DEX), in the treatment of breast cancer. We found that the administration of low-dose DEX suppressed tumor growth and distant metastasis in the MCF-7 and MDA-MB-231 xenograft mouse model, whereas treatment with high-dose DEX enhanced tumor growth and metastasis, respectively. Treatment of breast cancer cells with DEX inhibited cell adhesion, migration, and invasion in a dose-dependent manner. The DEX-mediated inhibition of cell adhesion, migration, and invasion is partly through induction of microRNA-708 and subsequent Rap1B-mediated signaling in MDA-MB-231 cells. On the other hand, in MCF-7 cells, DEX-suppressed cell migration is independent from microRNA-708 mediated signaling. Overall, our data reveal that DEX acts as a double-edged sword during breast-cancer progression and metastasis: Lower concentrations inhibit breast cancer tumor growth and metastasis, whereas higher concentrations may play an undesired role to promote breast cancer progression.

OBJECTIVE To provide better understanding of genetic susceptibility for health risk among current benzene-exposed workers. METHODS Four hundred sixty one benzene-exposed workers and 88 matched controls were recruited, and their benzene exposure doses were monitored. Associations between genetic susceptibility for polymorphisms of metabolic enzymes CYP2E1 and NQO1, and expression of cytokinesis-block micronucleus (MN) were investigated. RESULTS Mean MN frequency in the exposed workers was significantly higher than that in the control group (P

Ovarian cancer has the highest mortality rate among gynecologic malignancies. Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently with a poor prognosis. We previously reported a novel role of glucocorticoids (GCs) in metastatic ovarian cancer by upregulating microRNA-708. In this study, we used an immunocompetent syngeneic mouse model and further evaluated the effect and optimal dosages of GCs in treating metastatic ovarian cancer. The treatment of C57BL/6-derived ovarian cancer ID-8 cells with a synthetic GC, dexamethasone (DEX), induced the expression of microRNA-708, leading to decreased cell migration and invasion through targeting Rap1B. Administration of DEX at a low dose, as low as 5 μg/kg body weight, inhibited the primary tumor size and abdominal metastasis in mice bearing ID-8 cell-derived ovarian tumors. In the treated primary tumors, microRNA-708 was upregulated, whereas some proinflammatory cytokines, namely interleukin (IL)-1β and IL-18, were downregulated. The number of tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment were reduced. Overall, our study shows that low-dose GCs can suppress ovarian cancer progression and metastasis likely through not only the upregulation of the metastasis suppressor microRNA-708, but also the modulation of TAMs and MDSCs in the tumor microenvironment.

PURPOSE We used a rabbit model to evaluate the interface embedded between the recipient corneas and transplanted donor corneal discs after non-Descemet's stripping automated endothelial keratoplasty (nDSAEK). METHODS Unilateral DSAEK and nDSAEK surgeries were performed on New Zealand white rabbits. In vivo confocal microscopy was performed to show: the changes in corneal endothelial cells embedded between the recipient corneas and the transplanted donor corneal discs (CEEB); and the interface opacity by z profile. Immunohistochemistry were performed to evaluate the functional change of CEEB at post-nDSAEK 3 months. Transmission electron microscopy was performed to evaluate the morphology of CEEB after nDSAEK at post-nDSAEK 1, 3, and 6 months. RESULTS In vivo confocal microscopy showed a time-dependent decrease in the density of CEEB at postoperative 1, 2, or 3 months (P < 0.01). Interface opacity was higher in the nDSAEK group than the DSAEK group at all examination points, but the difference was statistically insignificant. At 3 months after surgery, the CEEB were negative for Na(+)/K(+)-ATPase staining. Staining with TUNEL showed apoptotic changes in some areas. During a 6-month observation, the CEEB showed a time-dependent thickening and loss of uniform thickness of cellular morphology. At 3 and 6 months post nDSAEK, extensions of the cellular processes into the donor graft stroma combined with intracellular vacuoles containing collagen-like materials were also found. CONCLUSIONS After non-Descemet's stripping automated endothelial keratoplasty, the CEEB showed decreased density, loss of pump function, apoptosis and changed morphology. However, the interface opacity was not significantly greater compared with DSAEK eyes.

To investigate the clinical characteristics and treatment outcomes of macular retinal detachment (MRD) associated with intrachoroidal cavitation (ICC) in myopic patients. In this retrospective, consecutive, interventional case series, five patients with ICC and associated MRD were enrolled from January 2005 to December 2012. Basic ocular characteristics and clinical appearances of their ICC and MRD were recorded. Individual treatment courses were assessed with fundus photographs and serial optical coherence tomography. The average age and refraction were 43.8 ± 11.0 years old and −9.37 ± 2.73 diopters, respectively. Initial BCVA ranged from 20/100 to 20/30. Definite communication between the ICC and the subretinal space was noted in one case, suspected curvilinear communication in two cases, and between the peripapillary area and the subretinal space in two cases. Two cases received intravitreal injection of perfluoropropane and peripapillary laser; subretinal fluid (SRF) resolved in one and decreased in the other. One case had SRF reabsorbed after prolonged use of topical carbonic anhydrase inhibitor. ICC in high myopic patients may be associated with MRD. There might be communication between the ICC and the subretinal space. Intravitreal injection of an expansile gas may be beneficial, but the best treatment remains undetermined.

Dysphagia is common after stroke. Neuromuscular electrical stimulation (NMES) and fiberoptic endoscopic evaluation of swallowing (FEES) for the treatment of dysphagia have gained in popularity, but the combined application of these promising modalities has rarely been studied. We aimed to evaluate whether combined NMES, FEES, and traditional swallowing rehabilitation can improve swallowing functions in stroke patients with moderate to severe dysphagia. Thirty-two patients with moderate to severe dysphagia poststroke (≥3 weeks) were recruited. Patients received 12 sessions of NMES for 1 h/day, 5 days/week within a period of 2–3 weeks. FEES was done before and after NMES for evaluation and to guide dysphagic therapy. All patients subsequently received 12 sessions of traditional swallowing rehabilitation (50 min/day, 3 days/week) for 4 weeks. Primary outcome measure was the Functional Oral Intake Scale (FOIS). Secondary outcome measures included clinical degree of dysphagia, the patient’s self-perception of swallowing ability, and the patient’s global satisfaction with therapy. Patients were assessed at baseline, after NMES, at 6-month follow-up, and at 2-year follow-up. Twenty-nine patients completed the study. FOIS, degree of dysphagia, and patient’s self-perception of swallowing improved significantly after NMES, at the 6-month follow-up, and at the 2-year follow-up (p < 0.001, each compared with baseline). Most patients reported considerable satisfaction with no serious adverse events. Twenty-three of the 29 (79.3 %) patients maintained oral diet with no pulmonary complications at 2-year follow-up. This preliminary case series demonstrated that combined NMES, FEES, and traditional swallowing rehabilitation showed promise for improving swallowing functions in stroke patients with moderate-to-severe dysphagia. The benefits were maintained for up to 2 years. The results are promising enough to justify further studies.

Background/Purpose Stargardt’s disease is the most common form of juvenile macular dystrophy. The purpose of this study is to report the clinical characteristics, visual function, and retinal tomography of patients diagnosed with Stargardt’s disease in Taiwan. Methods Retrospective case series; data collected include results of complete ophthalmic examinations: best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, fluorescein angiography, color sense discrimination test, electroculography (EOG), electroretinography (ERG), dark adaptation, visual field test, and optical coherence tomography (OCT) examinations focused on the macular area. Results Twenty patients were enrolled in this study. The mean age of the patients was 32.1 years. The mean logMAR-converted visual acuity of all patients was 0.96. Maculopathy with or without flecks was evident in all patients. Fluorescein angiography revealed hyperfluorescence in the macula of all cases. Varying degrees of color sense discrimination dysfunction were noted. Electrophysiologic studies showed subnormal to abnormal responses in most patients. Decreased foveal thickness was evident on OCT and foveal thickness was inversely associated with logMAR visual acuity. Also, logMAR visual acuity was associated with total error scores on the color sense discrimination test and the Arden ratio of EOG. The Arden ratio of EOG correlated with the thickness of the outer ring of the macula. Conclusion Typical clinical presentations of Stargardt’s disease were demonstrated in our case series. OCT findings showed a correlation between foveal thickness and visual acuity, making OCT a useful predictor for other visual function tests. Our results indicate that OCT is helpful in the evaluation of visual acuity and the progression of maculopathy in patients with Stargardt’s disease.

Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. l-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case-control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were .002 for all adenomas and

Purpose To report the incidence, microbiological profile, graft survival, and determining factors of microbial keratitis after penetrating keratoplasty (PK). Design Observational case series. Methods The study involved 51 patients (52 eyes) who were treated at a single tertiary referral center during a 10-year period. Retrospective chart review included medical records of all patients diagnosed with microbial keratitis after penetrating keratoplasty at the National Taiwan University Hospital between January 2000 and December 2009. The main outcome measures were incidence of graft infection, microbial profile, and graft survival status. Results There were 871 PKs performed and 67 episodes in 52 eyes of culture-positive microbial keratitis during the study period. There were 32 infectious episodes (47.8%) in the first year post-PK and 35 episodes (52.2%) after the first year post-PK. Forty-four gram-positive bacterial isolates (57.9%), 17 gram-negative bacterial isolates (22.4%), and 15 fungal isolates (19.7%) were found. Twenty-three (34.3%) grafts remained clear after the infection episode with a mean follow-up of 1127 days (range, 25–3962 days). There was no difference in graft survival rate regarding the original indication of PK or offending pathogen. Suture-related infection was associated with decreased risk of graft failure ( P = .02), while the factor associated with increased risk of graft failure was usage of antiglaucoma agents ( P = .01). Conclusion Infectious keratitis after penetrating keratoplasty leads to a high graft failure rate. Such complications can occur before or after the first year post-PK.

This study is to determine the distribution of the delta-aminolevulinic acid dehydratase (ALAD) polymorphism among Han subjects of the Chinese population and to study whether the polymorphism in the ALAD gene modifies the toxicity of lead in lead-exposed workers. For this purpose we conducted a cross-sectional study on 156 Chinese workers who were exposed to lead in lead-acid battery and electric-flex manufacturing plants. The authors found that the allele frequencies of ALAD1 and ALAD2 were 0.9679 and 0.0321, respectively. Workers with the ALAD 1-1 genotype were associated with higher blood lead levels than those with the ALAD 1-2 genotype. Blood and urine lead levels were much higher in storage battery workers than in cable workers. The self-conscious symptom survey showed that the incidences of debilitation, amnesia and dreaminess were much higher in those had more than five years of tenure or contact with lead on the job within the ALAD 1-1 genotype subgroup. Laboratory examinations showed that serum iron and zinc levels in workers’ with the ALAD 1-2 genotype were higher than those with the ALAD 1-1 genotype, especially in storage-battery workers. Correlation analysis indicated that the blood lead level negatively correlated with serum calcium, iron and zinc level. The data of this study suggest that the ALAD gene polymorphism and serum ion levels may modify the kinetics of lead in blood. Therefore, the authors recommend that an adequate intake of dietary calcium, iron, and zinc or the calcium, iron, and zinc supplementation should be prescribed to Chinese lead exposed workers.

OBJECTIVE To evaluate the expressions of p53, p21, and CCND1 in the peripheral blood lymphocytes of vinyl chloride monomer (VCM)-exposed workers and potential relationships with their exposures, polymorphisms, and chromosomal aberrations. METHODS The study was performed on 77 occupationally VCM-exposed workers and 43 unexposed controls. The quantities of mRNA expression of p53, p21, and CCND1 genes were detected by real-time polymerase chain reaction. RESULTS p53 mRNA expression of VCM-low- and high-exposure groups was significantly lower than that of nonexposed group (P < 0.001), but p21 mRNA expression of the two VCM-exposed groups was significantly higher than that of the nonexposed group (P < 0.001). This study did not find the relationship between chromosomal aberrations, genotypes, and the expression of p53, p21, and CCND1. CONCLUSIONS Messenger RNA expressions of p53 and p21 are changed with VCM-exposure status.

BACKGROUND Ankle arthritis can cause substantial pain and functional limitation. Previous studies have indicated that five weekly intra-articular injections of hyaluronate were safe and effective in the treatment of ankle osteoarthritis. The purpose of this study was to evaluate the effect and safety of three weekly injections of hyaluronate in patients with unilateral ankle arthritis. METHODS Fifty patients who had had unilateral ankle pain for at least six months and were classified radiographically as having Kellgren-Lawrence grade-2 or 3 ankle arthritis were recruited for a prospective study. Patients received three weekly intra-articular injections of hyaluronate. The primary outcome was the change in the Ankle Osteoarthritis Scale score at six months after the third injection. Secondary outcomes included the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Score, four clinical tests of balance, consumption of rescue analgesics, and global patient satisfaction. RESULTS Forty-six participants completed the study. A significant reduction in the mean Ankle Osteoarthritis Scale score was noted at one, three, and six months after the third injection (p < 0.05 for each follow-up visit compared with baseline). The mean AOFAS Ankle-Hindfoot Score improved from 60.5 points at baseline to 73.5, 75.5, and 76.7 points at one, three, and six months of follow-up, respectively (p < 0.05). The patients demonstrated significant improvement on all four balance tests at each follow-up visit (p < 0.05 for each test compared with baseline). Acetaminophen consumption dropped significantly following treatment (p < 0.05). The patients' satisfaction rate was high, and no serious adverse events were reported. CONCLUSIONS This study suggests that three weekly injections of hyaluronate are well-tolerated and can provide pain relief and improve function and balance in patients with unilateral ankle arthritis. Larger controlled trials with longer follow-up are necessary to verify the effects of hyaluronate in the treatment of ankle arthritis.

Benzene reactive metabolites can lead to DNA damage and trigger the p53-dependent defense responses to maintain genomic stability. We hypothesized that the p53-dependent genes may play a role in the development of chronic benzene poisoning (CBP). In a case-control study of 303 patients with benzene poisoning and 295 workers occupationally exposed to benzene in south China, we investigated associations between the risk of CBP and polymorphisms in three p53-dependent genes. Potential interactions of these polymorphisms with lifestyle factors were also explored. We found p14(ARF) rs3731245 polymorphism was associated with risk of CBP (P=0.014). Compared with those carrying the GG genotype, individuals carrying p14(ARF) rs3731245 GA+AA genotypes had a reduced risk of CBP ([adjusted odds ratio (OR(adj))=0.57, 95%CI=0.36-0.89]. Further analysis showed p14(ARF) TGA/TAG diplotype was associated with an increased risk of CBP (P=0.0006), whereas p14(ARF) TGG/TAA diplotype was associated with a decreased risk of CBP (P=0.0000001). In addition, we found individuals carrying both MDM2 Del1518 WW genotype and p14(ARF) rs3731245 GA+AA genotypes had a lower risk of CBP (OR(adj)=0.25; 95%CI=0.10-0.62; P=0.003). Although these results require confirmation and extension, our findings suggest that genetic polymorphisms in p14(ARF) may have an impact on the risk of CBP in the study population.

Background and objective . Botulinum toxin type A (BtxA) injection and modified constraint-induced movement therapy (mCIMT) are both promising approaches to enhance recovery after stroke. The combined application of these 2 promising modalities has rarely been studied. The aim was to investigate whether combined BtxA and mCIMT would improve spasticity and upper extremity motor function more than BtxA plus conventional rehabilitation in chronic stroke patients with upper extremity spasticity. Methods. In a prospective, randomized controlled, observer-blinded trial with 6-month follow-up, 32 patients (≥1 year after stroke) with ability to actively extend >10° at metacarpophalangeal and interphalangeal joints and 20° at wrist of the affected upper limb were randomized to receive BtxA + mCIMT (combination group) or BtxA + conventional rehabilitation (control group) for 2 hours/day, 3 days/week for 3 months.The primary outcome assessed spasticity on the Modified Ashworth Scale. Secondary outcomes assessed real-world arm function (Motor Activity Log), laboratory motor activity (Action Research Arm Test), and patients’ global satisfaction. Results. A total of 32 stroke patients were recruited, and 29 completed the study. Spasticity significantly improved in all subjects at 4 weeks and 3 months postinjection without between-group differences.The combination group showed significantly greater improvements in elbow, wrist, and finger spasticity ( P = .019, P = .019, and P < .001, respectively), affected upper extremity real-world arm function ( P < .001) and laboratory motor activity ( P < .001) than the control group at 6-month postinjection. Patients reported considerable satisfaction and no serious adverse events occurred. Conclusions. Combining BtxA and mCIMT is an effective and safe intervention for improving spasticity and motor function in chronic stroke patients. The results are promising enough to justify further studies. We recommend future research to address the likely need for including rehabilitation with BtxA to improve function in patients with poststroke spasticity.

DNA damage induced by benzene reactive metabolites is thought of as an important mechanism underlying benzene hematotoxicity and genotoxicity, and genetic variation in cell-cycle control genes may contribute to susceptibility to chronic benzene poisoning (CBP). Using a case-control study that included 307 benzene-poisoned patients and 299 workers occupationally exposed to benzene in south China, we aimed to investigate the association between genetic polymorphisms of p53 and p21 and the odds of CBP. To investigate whether benzene exposure may influence mRNA expression of p53 and p21 in benzene-exposed workers, we also chose 39 CBP workers, 38 occupationally benzene-exposure workers, and 37 nonexposure workers in the same region of China. PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53 (rs17878362, rs1042522, and rs1625895) and p21 (rs1801270 and rs1059234), and real-time PCR was applied to detect the quantity of gene mRNA expression. We found that p21 C98A variant genotypes (CA+AA) or C70T variant genotypes (CT+TT) were associated with decreased odds of CBP [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.32-0.83, and OR, 0.53; 95% CI, 0.29-0.95, respectively. Further analysis showed the decreased odds of CBP in the subjects with p21 CC/AT diplotype (OR, 0.51; 95% CI, 0.30-0.85). In addition, p53 mRNA expression of CBP workers or benzene-exposure workers was significantly lower than that of nonexposure workers. Although these results require confirmation and extension, our results show that polymorphisms in p21 may be protective against the risk of CBP in the Chinese occupational population. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1821–8)

It is widely accepted that the cytotoxicity and genotoxicity of benzene results from the action of reactive metabolites. Therefore, genetic variation in metabolic enzyme genes may contribute to susceptibility to chronic benzene poisoning (CBP) in the exposed population. Using a case-control study that included 268 benzene-poisoned patients and 268 workers occupationally exposed to benzene in South China, we aimed to investigate the association between single-nucleotide polymorphisms in genes with phase I and II of metabolism and risk of CBP. The TaqMan technique was used to detect polymorphisms of CYP1A1, CYP1A2, CYP1B1, ADH1B, EPHX1, EPHX2, NQO1, MPO, GSTP1 and UGT1A6 genes. We also explored potential interactions of these polymorphisms with lifestyle factors such as cigarette smoking and alcohol consumption. A weak positive association was found between glutathione S-transferase pi-1 (GSTP1) rs1695 polymorphism and the risk of CBP (P = 0.046), but this association was not statistically significant (P = 0.117) after adjustment for potential confounders. Further analysis showed that the risk of CBP increased in the subjects with EPHX1 GGAC/GAGT diplotype (P = 0.00057) or AGAC/GAGT diplotype (P = 0.00086). In addition, we found that alcohol drinkers with the EPHX1 rs3738047 GA + AA genotypes and non-alcohol drinkers with the GSTP1 rs1695 AA genotype tended to be more susceptible to benzene toxicity. Our results suggest that genetic polymorphisms in EPHX1 may contribute to risk of CBP in a Chinese occupational population.

Genetic variations in metabolic enzyme genes may enhance hematotoxicity in benzene-exposed populations.To investigate the association between polymorphisms of metabolism genes and white blood cells (WBCs).Three hundred and eighty-five benzene-exposed workers and 220 unexposed indoor workers were recruited in China. We explored the relationship between metabolic enzymes polymorphisms [glutathione S-transferase T1/M1 (GSTT1/M1) null, glutathione S-transferase P1 (GSTP1)rs1695, Cytochrome P450 2E1 (CYP2E1) rs3813867, rs2031920, rs6413432, microsomal epoxide hydrolase (mEH) rs1051740, rs2234922] by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis and WBC.The exposed group had lower WBC counts (P0·001) than the unexposed group. Increased susceptibility to hematotoxicity, as evidenced by lower WBC counts, was found in workers with null-GSTT1 (P = 0·045), null-GSTM1 (P = 0·030), rs2031920 (P = 0·020), and rs3813867 (P = 0·014) genotypes. White blood cell counts were also lower in workers with null-GSTT1 and null-GSTM after adjusting for age, gender, smoking, and alcohol consumption.Null-GSTT1 and null-GSTM1 genotypes and Cytochrome P4502E1 (CYP2E1: rs2031920, rs3813867) may support the hematotoxicity of benzene-exposed workers in China, and we can make use of it to select susceptible population.

Glucocorticoids are widely used in conjunction with chemotherapy for ovarian cancer to prevent hypersensitivity reactions. Here we reveal a novel role for glucocorticoids in the inhibition of ovarian cancer metastasis. Glucocorticoid treatments induce the expression of miR-708, leading to the suppression of Rap1B, which result in the reduction of integrin-mediated focal adhesion formation, inhibition of ovarian cancer cell migration/invasion and impaired abdominal metastasis in an orthotopic xenograft mouse model. Restoring Rap1B expression reverts glucocorticoid-miR-708 cascade-mediated suppression of ovarian cancer cell invasion and metastasis. Clinically, low miR-708 and high Rap1B are found in late-state ovarian tumours, as compared with normal, and patients with high miR-708 show significantly better survival. Overall, our findings reveal an opportunity for glucocorticoids and their downstream mediators, miR-708 or Rap1B, as therapeutic modalities against metastatic ovarian epithelial cancer., Glucocorticoids show promise for the treatment of ovarian cancer. Here the authors show that glucocorticoids transcriptionally induce the tumour suppressor miR-708, which is downregulated in ovarian cancer, especially in late stages and metastatic tumours.

Background We investigated the clinical value of Doppler echocardiography for determining the optimal setting of atrioventricular interval in patients with dual chamber pacemakers (DDD). In 38 patients with complete atrioventricular block and DDD pacemakers, the atrioventricular interval was prolonged in a stepwise fashion by 20 ms, from 90 to 250 ms, and cardiac stroke volume and transmitral flow were measured by pulsed Doppler echocardiography. Methods The optimal atrioventricular interval at which the cardiac stroke volume was maximal was 168.9 ± 15.6 ms. The atrioventricular interval was 178.4 ± 23.4 ms when the end of the A wave coincided with complete closure of the mitral valve. Results There was a significant linear relationship between the optimal atrioventricular interval and the predicted optimal atrioventricular interval (Y = 86.2 ± 0.5X, r = 0.70, standard error of the estimate [SEE] = 11.5, P < 0.01). Conclusion The optimal atrioventricular interval setting for DDD pacing can be successfully determined using Doppler echocardiography, which is a noninvasive, repeatable, and simple approach. Copyright © 2009 Wiley Periodicals, Inc.

Objective: To explore the association of the methylation status of MGMT and hMLH1 with chromosome damage induced by vinyl chloride monomer (VCM). Materials and Methods: Methylation of MGMT and hMLH1 was measured in 101 VCM-exposed workers by methylation-specifi c PCR. Chromosome damage in peripheral blood lymphocytes was measured by the cytokinesis-block micronucleus assay. The subjects were divided into chromosome damaged and non-damaged groups based on the normal reference value of micronuclei frequencies determined for two control groups. Results: MGMT promoter methylation was detectable in 5 out of 49 chromosome damaged subjects, but not in the chromosome non-damaged subjects; there was a signifi cant difference in MGMT methylation between the two groups (p < 0.05). Conclusions: We detected aberrant promoter methylation of MGMT in a small number of chromosome damaged VCM-exposed workers, but not in the chromosome non-damaged subjects. This preliminary observation warrants further investigation in a larger study.

To examine the surgical results of lamellar macular hole (LMH) secondary to epiretinal membrane (ERM). A 3-year retrospective review was performed of patients with LMH secondary to ERM that underwent ERM and internal limiting membrane (ILM) peeling. The main outcome measures included best-corrected visual acuity (BCVA) and postoperative macular structure. The results were compared with cases of idiopathic ERM with similar baseline demographic characteristics. Thirty eyes in 30 patients were collected. The mean BCVA improvement was 3.4 Snellen lines after a mean follow-up period of 16.9 months. Optical coherence tomography (OCT) showed improved macular contour in 27 cases. Patients with intravitreal gas tamponade exhibited a higher percentage of restoration of macular contour than those without (P = 0.016). Final BCVA was correlated with an intact photoreceptor inner segment–outer segment (IS–OS) junction (P = 0.03). The degree of visual improvement is less than that observed in idiopathic ERM patients. In LMH secondary to ERM with significant visual decrease, ERM and ILM peeling may improve BCVA. Postoperative gas tamponade is associated with better restoration of macular configuration. Final BCVA is related to an intact photoreceptor IS–OS junction rather than to the normalization of the macular contour.

Objective We investigated how cells respond to the induction of DNA damage, focusing specifically on mRNA expression levels of cell regulatory and DNA repair genes under exposure to benzene. Method The study sample was classified into three groups: direct exposure to benzene (A), indirect exposure to benzene (B), and non-exposed (C). Concentrations of benzene in the air of workplaces were monitored. Further blood biochemical parameters, cell cycle-regulated and DNA damage-related genes expression were analyzed. Results The mRNA expression levels of Apel, Rad51, Bcl-2, Bax, Xpa, and Xpc genes were significantly down-regulated in groups A and B, with a dramatic up-regulation of p21 gene in group A accompanied by significantly lower counts of white blood cells, hemoglobin, platelets and lymphocyte subsets of CD8+, CD4+, T and B cells. Conclusion The results indicated that exposure to benzene had significantly altered mRNA expression of some critical cell regulatory and DNA repair genes.

To explore the association of polymorphisms of metabolizing enzyme genes with chronic benzene poisoning (CBP) comprehensively by case-control design.152 CBP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. 30 single nucleotide polymorphisms (SNPs) in 13 genes such as CYP2E1 were tested by PCR-RFLP, sequencing approaches. Logistic regression model was used to detect main effects and 2-order interaction effects of gene and/or environment. Multifactor dimensionality reduction (MDR) was used to detect high-order gene-gene or gene-environment interactions.Based on logistic regression, the main effects of GSTP1 rs947894, EPHX1 rs1051740, CYP1A1 rs4646903, CYP2D6 rs1065852 and rs1135840 were found to be significant (P0.05) while the confounding factors of sex, cigarette smoking, alcohol consumption and the intensity of benzene exposure were controlled. EPHX1 rs1051740 might be associated with CBP (P = 0.06). There existed 3 types of interactions were as followed: interactions of GSTP1 rs947894 with alcohol consumption, CYP2E1 rs3813867 with EPHX1 rs3738047, EPHX1 rs3738047 with alcohol consumption(P0.05), while the main effects of CYP2E1 rs3813867 and EPHX1 rs3738047 were not significant (P0.05). The other SNPs did not show any significant associations with CBP. According to MDR, a 3-order interaction with the strongest combined effect was found, i.e. the 3-factor combination of CYP1A1 rs4646903, CYP2D6 rs1065852 and CYP2D6 rs1135840.Gene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.

Vinyl chloride monomer (VCM) is genotoxic and cancerogen agent. Individual variations in response to the exposure have been noticed and the variations may be due to genetic differences in the removal of VCM-DNA adducts, such as polymorphism in genes NER pathway and BER pathway. This study explores the relationship between genetic polymorphism of seven genes within the NER pathway (XPA, XPD, XPC, XPG, XPF, and ERCC1) and BER pathway (APE1), and susceptibility to chromosomal damage after exposure to VCM. One hundred and eighty workers occupationally exposed to VCM and 43 unexposed controls were investigated. Chromosome damage in peripheral lymphocytes was measured by the cytokinesis-blocked micronucleus assay. PCR-RFLP technique was applied to detect polymorphisms of the seven genes. The influence of genotype, age, gender, cumulative exposure dose, alcohol consumption, and smoking status on the frequencies of MN was determined using univariate and multiple Poisson regression analyses. We found XPA A23G variant workers had significantly higher MN frequencies than those from the wild-type homozygous counterparts (P = 0.01). Those with the variant XPD Lys751Gln genotype had marginally higher MN frequencies (P = 0.07). On the other hand, XPC PAT and XPF 5'-UTR T2063A variant workers had significantly lower MN frequencies compared with those from their wild-type homozygous counterparts (P = 0.04 and P = 0.004, respectively). Our findings suggest that XPC PAT, XPD Lys751Gln, XPA A23G and XPF 5'-UTR T2063A contribute to the level of chromosome damage in occupational exposure to VCM in Chinese population.

To explore the relation between genetic polymorphisms in XPD and risks of chronic benzene poisoning (CBP).A case-control study was conducted. 152 CBP patients and 152 NCBP workers occupationally exposed to benzene were investigated. Polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) at c. 199, c. 201, c. 312 and c. 751 of XPD gene.No variant alleles was detected at c. 199 and c. 201 of XPD gene. In comparition with the individual genotypes of XPDc. 312Asp/Asp, the risk of CBP suffered from the individual genotype of XPDc. 312Asp/Asn + Asn/Asn decreased a 0.59 fold (ORadj = 0.59, 95% CI = 0.35-0.99, chi2 = 3.99, P0.05), when sex, workage and intensity of benzene exposure were adjusted. And in low intensity of benzene exposure group, the risk of CBP suffered from the individual genotypes of XPDc. 312Asp/Asn + Asn/Asn more decreased (ORadj = 0.13, 95% CI = 0.04-0.51, chi2 = 8.93, P0.01).Polymorphism of XPD Asp312Asn could contribute to altered risk of CBP.

To investigate the association between genetic polymorphisms in phase I and phase II metabolism genes and DNA damage in peripheral blood lymphocytes of workers exposed to vinyl chloride monomer (VCM).87 workers occupationally exposed to VCM were investigated. DNA damage in peripheral blood lymphocytes was measured by Comet Assay; the workers were divided into case, control groups based on the comet frequency. Genotypes of CYP2E1 (rs3813867) were identified by the PCR-RFLP, null genotypes of GSTT1 and GSTM1 were detected by PCR. The genotype of GSTP1 (rs947894), CYP1A1 (rs1048943, rs4646903) and UGT1A6 (rs6759892, rs1105879, rs4124874, rs3755319, rs887829, rs4148323) were tested by the TaqMan PCR method.The distribution of the c1c1 and c1c2 + c2c2 genotype of CYP2E1 (rs3813867), AA and AG + GG genotype of GSTP1 (rs947894), AA and AC + CC genotype of UGT1A6 (rs1105879) were significantly different in DNA damage group and control group by chi2 test (P = 0.029, P = 0.004 and P = 0.002, respectively). Multiple logistic regression analysis showed that the individuals carrying GSTP1 (rs947894) AG + GG genotypes had 13.393-fold (95% CI: 2.410-74.431, P0.01) increased risk of DNA damage in comparison with those with GSTP1 AA genotypes, and individuals carrying UGT1A6 (rs1105879) AC + CC genotypes had 0.064-fold (95% CI: 0.006-0.637, P0.05) decreased risk of DNA damage in comparison with those with UGT1A6 (rs1105879) AA genotypes. Haplotypes analysis of polymorphisms in UGT1A6 showed that the frequencies of TCCTAG haplotype in the controls were significant higher than those in the cases (P0.05).The subjects carrying GSTP1rs947894 AG/GG genotypes and UGT1A6 rsl105879 AA genotypes could be more susceptible to VCM-induced DNA damage. UGT1A6 TCCTAG haplotype may be a protective genetic factor for DNA damage in VCM-exposed workers.

This study explores the relationship between genetic polymorphisms of p53, p21, and CCND1, and the susceptibility of chromosomal damage induced by vinyl chloride monomer (CH2 = CHCl, VCM). Besides gene polymorphisms, we detected the mRNA expression of p53, p21, and CCND1 in VCM-exposed workers and in a control group. One hundred and eighty-three workers occupationally exposed to VCM were investigated. Chromosome damage in peripheral lymphocyte was measured by cytokinesis-block micronucleus assay. The PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53, p21 (exon 2 and exon 3), and CCND1 genes (exon 4). The quantity of gene mRNA expression was detected by real-time PCR (SYBR Green I). Taking into account the effects of genetic polymorphisms, as well as demographic and habitual factors, Poisson regression analysis showed that the risk of chromosomal damage induced by VCM for individuals carrying the p53 intron 6 heterozygous and mutant homozygous genotype was 1.23 times larger (90% confidence interval, 1.01-1.51 P = 0.0814), compared with those carrying wild-type homozygous genotypes. The p53 exon 4, intron 3, and intron 6 haplotype pairs of MMM/WWW (M, mutation allele; W, wild allele), and MWM/WWW were associated with increased frequencies of micronuclei. The p53 mRNA expression of VCM-exposed workers was significantly lower than that of nonexposed workers, but p21 mRNA expression in VCM-exposed workers was significantly higher than that of nonexposed workers. Our findings suggest that the p53 intron 6 polymorphism is one of the factors that potentially influence the frequency of micronuclei induced by VCM. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2578–84)

The familial variant of cardiac myxoma is known to be an autosomally dominant disease. Early diagnosis, and removal of the tumours, are of great importance. In this regard, echocardiography is considered the simplest and most reliable diagnostic method. We report our experience with echocardiographic diagnosis of a family with atrial myxomas.

To explore the relationship between genetic polymorphisms in MPO, NQO1, GSTP1, UGT1A6 and susceptibility to chronic benzene poisoning (BP).A case-control study was conducted. 268 BP patients and 268 workers occupationally exposed to benzene without poisoning manifestations were investigated. The genotype of MPO (rs7208693), NQO1 (rs1800566), GSTP1 ( rs947894 ) and UGT1A6 (rs6759892, rs1105879, rs4124874 ,rs3755319 ,rs887829 and rs4148323) were tested by the TaqMan PCR method.There was a 0.675-fold (95% CI 0.434 - 0.994, P = 0.046) decreased risk of BP in the subjects with GSTP1 rs947894 G alleles compared with those carrying AA genotype. In the subjects carrying allele of MPO rs7208693 A, the risk of BP increased for the individuals carrying allele of UGT1A6 rs6759892 G (OR = 2.702, P = 0.024) compared to those with TT genotype or the individusals carrying allel of UGT1A6 rs1105879 C (OR = 2.619, P = 0.035) compared to those with TT genotype. In drinking population, the individuals carrying the NQO1 rs1800566 TT homozygote genotype had a 9.000-fold (5% CI 1.460 - 55.478, P = 0.021) risk of BP compared to those with CT + CC genotypes. In smoking population, there was 7.000-fold (95% CI 1.555 - 31.575, P = 0.012) of risk in BP subjects carrying NQO1 rs1800566T/T genotype, compared with those carrying CC + CT genotype. Haplotyes analysis of polymorphisms in UGT1A6 showed that compared with those carrying TAATGG haplotype, there was a 1.446-fold (OR = 1.446, 95% CI 1.005 - 2.080, P = 0.046) increased risk of BP for those carrying TACGGG haplotype.The subjects carrying allele of MPO rs7208693 A and UGT1A6 rs6759892 G or rs1105879 C at the same time could be more susceptible to BP. The subjects carrying NQO1 rs1800566 TT genotype and together with the habit of smoking or drinking could be more susceptible to BP. Those subjects carrying TAATGG haplotype of UGT1A6 could increase the risk of BP. Further studies should be needed on the association between the genetic polymorphisms in GSTP1 and the risk of BP.

Introduction: Aortopulmonary window (APW), a large aortopulmonary septal defect (APSD), is a serious and rare defect within congenital heart diseases. Case report: In this study, we reported an APW case with severe pulmonary arterial hypertension. This patient was successfully treated by transcatheter closure with a muscular ventricular septal defect (VSD) occluder. Conclusion: We had a successful experience with transcatheter closure of a large APW using a muscular VSD occluder. There was no residual shunt or complications during the 6-month follow-up.