Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Risk factors for the mortality of hemodialysis patients with COVID-19: A multicenter study from the overall hemodialysis population in Wuhan.

INTRODUCTION: Maintenance hemodialysis (MHD) patients are highly threatened in the novel coronavirus disease 2019 (COVID-19) pandemic, but evidence of risk factors for mortality in this population is still lacking. METHODS: We followed outcomes of the overall MHD population of Wuhan, including 7154 MHD patients from 65 hemodialysis centers, from January 1 to May 4, 2020. Among them, 130 were diagnosed with COVID-19. The demographic and clinical data of them were collected and compared between survivors and nonsurvivors. RESULTS: Compared to the corresponding period of last year, the all-cause mortality rate of the Wuhan MHD population significantly rose in February, and dropped down in March 2020. Of the 130 COVID-19 cases, 51 (39.2%) were deceased. Advanced age, decreased oxygen saturation, low diastolic blood pressure (DBP) on admission, and complications including acute cardiac injury (HR 5.03 [95% CI 2.21-11.14], p < 0.001), cerebrovascular event (HR 2.80 [95% CI 1.14-6.86], p = 0.025) and acute respiratory distress syndrome (HR 3.50 [95% CI 1.63-7.51], p = 0.001) were identified as independent risk factors for the death of COVID-19. The median virus shedding period of survivors was 25 days, longer than the general population. CONCLUSIONS: Maintenance hemodialysis patients are a highly vulnerable population at increased risk of mortality and prolonged virus shedding period in the ongoing COVID-19 pandemic. Advanced age, decreased oxygen saturation, low DBP on admission, and complications like acute cardiac injury are parameters independently associated with poor prognosis.

Serum concentrations of organochlorine pesticides, biomarkers of oxidative stress, and risk of breast cancer.

Studies have documented that exposure to organochlorine pesticides (OCPs) is linked with breast cancer, but the underlying biological mechanisms are still unknown. This study included 313 women diagnosed with breast cancer and 313 controls in Wuhan, China, and measured 18 OCPs in serum and 3 oxidative stress biomarkers in urine. Multivariable adjusted regression models were used to evaluate the associations among OCPs, oxidative stress biomarkers, and breast cancer. The mediating effect of oxidative stress was assessed by mediation analysis. We observed that most OCPs were positively associated with risk of breast cancer (all FDR-P values < 0.05 or 0.10). Moreover, we found that p,p'-DDT, p,p'-DDD, dieldrin, heptachlor, and heptachlor epoxide were positively associated with 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-iso-prostaglandin F2α (8-isoPGF2α), which in turn were positively associated with risk of breast cancer. Mediation analysis indicated that HNE-MA and 8-isoPGF2ɑ mediated the positive associations between these OCPs and risk of breast cancer, with mediating proportion ranging from 6.23% to 19.9%. Our results suggest that lipid peroxidation may mediate the positive associations between OCP exposures and risk of breast cancer.

Serologic Detection of SARS-CoV-2 Infections in Hemodialysis Centers: A Multicenter Retrospective Study in Wuhan, China.

RATIONALE & OBJECTIVE: Patients receiving maintenance hemodialysis (MHD) are highly vulnerable to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current study was designed to evaluate the prevalence of SARS-CoV-2 infection based on both nucleic acid testing (NAT) and antibody testing in Chinese patients receiving MHD. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: From December 1, 2019, to March 31, 2020, a total of 1,027 MHD patients in 5 large hemodialysis centers in Wuhan, China, were enrolled. Patients were screened for SARS-CoV-2 infection by symptoms and initial computed tomography (CT) of the chest. If patients developed symptoms after the initial screening was negative, repeat CT was performed. Patients suspected of being infected with SARS-CoV-2 were tested with 2 consecutive throat swabs for viral RNA. In mid-March 2020, antibody testing for SARS-CoV-2 was obtained for all MHD patients. EXPOSURE: NAT and antibody testing results for SARS-CoV-2. OUTCOMES: Morbidity, clinical features, and laboratory and radiologic findings. ANALYTICAL APPROACH: Differences between groups were examined using t test or Mann-Whitney U test, comparing those not infected with those infected and comparing those with infection detected using NAT with those with infection detected by positive serology test results. RESULTS: Among 1,027 patients receiving MHD, 99 were identified as having SARS-CoV-2 infection, for a prevalence of 9.6%. Among the 99 cases, 52 (53%) were initially diagnosed with SARS-CoV-2 infection by positive NAT; 47 (47%) were identified later by positive immunoglobulin G (IgG) or IgM antibodies against SARS-CoV-2. There was a spectrum of antibody profiles in these 47 patients: IgM antibodies in 5 (11%), IgG antibodies in 35 (74%), and both IgM and IgG antibodies in 7 (15%). Of the 99 cases, 51% were asymptomatic during the epidemic; 61% had ground-glass or patchy opacities on CT of the chest compared with 11.6% among uninfected patients (P<0.001). Patients with hypertensive kidney disease were more often found to have SARS-CoV-2 infection and were more likely to be symptomatic than patients with another primary cause of kidney failure. LIMITATIONS: Possible false-positive and false-negative results for both NAT and antibody testing; possible lack of generalizability to other dialysis populations. CONCLUSIONS: Half the SARS-CoV-2 infections in patients receiving MHD were subclinical and were not identified by universal CT of the chest and selective NAT. Serologic testing may help evaluate the overall prevalence and understand the diversity of clinical courses among patients receiving MHD who are infected with SARS-CoV-2.

[Producing Coefficients and Emission Coefficients of Volatile Organic Compounds from the Automobile Manufacturing Industry in Zhejiang Province].

Four typical automobile manufacturing enterprises in Zhejiang Province were selected to determine the main production and emission links of volatile organic compounds (VOCs) in this industry by analyzing their production processes and the main raw and auxiliary materials used. Two of them were monitored on the spot, and the producing coefficients and emission coefficients of the VOCs discharged from the automobile manufacturing industry in Zhejiang Province were calculated. Then, the production and emission of VOCs in this industry in 2017 in Zhejiang Province were estimated. The results show that the main production and emission links of VOCs in the automobile manufacturing industry in Zhejiang Province are coating processes. Only a few of the automobile manufacturers in Zhejiang Province can deal with the paint exhaust gas effectively at present; in addition to coatings, solvent-based cleaning agents are also one of the main sources of VOCs in this industry. The VOC producing coefficients of the automobile manufacturing industry in Zhejiang Province are 0.20 t·t-1, 3.92 kg·vehicle-1, and 29.36 g·m-2; the emission coefficients are 0.13 t·t-1, 2.63 kg·vehicle-1, and 19.72 g·m-2. The quantity of VOCs generated by this industry in 2017 was 2425.84 t, while the quantity of emissions was 1627.54 t.

Potential of Arbidol for Post-exposure Prophylaxis of COVID-19 Transmission: A Preliminary Report of a Retrospective Cohort Study.

The efficient transmission of severe acute respiratory syndrome-2 coronavirus (SARS-CoV-2) from patients to health care workers or family members has been a worrisome and prominent feature of the ongoing outbreak. On the basis of clinical practice and in-vitro studies, we postulated that post-exposure prophylaxis (PEP) using Arbidol is associated with decreased infection among individuals exposed to confirmed cases of COVID-19 infection. We conducted a retrospective cohort study on family members and health care workers who were exposed to patients confirmed to have SARS-CoV-2 infection by real-time RT-PCR and chest computed tomography (CT) from January 1 to January 16, 2020. The last follow-up date was Feb. 26, 2020. The emergence of fever and/or respiratory symptoms after exposure to the primary case was collected. The correlations between post-exposure prophylaxis and infection in household contacts and health care workers were respectively analyzed. A total of 66 members in 27 families and 124 health care workers had evidence of close exposure to patients with confirmed COVID-19. The Cox regression based on the data of the family members and health care workers with Arbidol or not showed that Arbidol PEP was a protective factor against the development of COVID-19 (HR 0.025, 95% CI 0.003-0.209, P=0.0006 for family members and HR 0.056, 95% CI 0.005-0.662, P=0.0221 for health care workers). Our findings suggest Arbidol could reduce the infection risk of the novel coronavirus in hospital and family settings. This treatment should be promoted for PEP use and should be the subject of further investigation.

Clinical Characteristics of and Medical Interventions for COVID-19 in Hemodialysis Patients in Wuhan, China.

BACKGROUND: Reports indicate that those most vulnerable to developing severe coronavirus disease 2019 (COVID-19) are older adults and those with underlying illnesses, such as diabetes mellitus, hypertension, or cardiovascular disease, which are common comorbidities among patients undergoing maintenance hemodialysis. However, there is limited information about the clinical characteristics of hemodialysis patients with COVID-19 or about interventions to control COVID-19 in hemodialysis centers. METHODS: We collected data retrospectively through an online registration system that includes all patients receiving maintenance hemodialysis at 65 centers in Wuhan, China. We reviewed epidemiologic and clinical data of patients with laboratory-confirmed COVID-19 between January 1, 2020 and March 10, 2020. RESULTS: Of 7154 patients undergoing hemodialysis, 154 had laboratory-confirmed COVID-19. The mean age of the 131 patients in our analysis was 63.2 years; 57.3% were men. Many had underlying comorbidities, with cardiovascular disease (including hypertension) being the most common (68.7%). Only 51.9% of patients manifested fever; 21.4% of infected patients were asymptomatic. The most common finding on chest computed tomography (CT) was ground-grass or patchy opacity (82.1%). After initiating comprehensive interventions-including entrance screening of body temperature and symptoms, universal chest CT and blood tests, and other measures-new patients presenting with COVID-19 peaked at 10 per day on January 30, decreasing to 4 per day on February 11. No new cases occurred between February 26 and March 10, 2020. CONCLUSIONS: We found that patients receiving maintenance hemodialysis were susceptible to COVID-19 and that hemodialysis centers were high-risk settings during the epidemic. Increasing prevention efforts, instituting universal screening, and isolating patients with COVID-19 and directing them to designated hemodialysis centers were effective in preventing the spread of COVID-19 in hemodialysis centers.

Urinary biomarkers of phthalates exposure and risks of thyroid cancer and benign nodule.

Phthalates have been reported to affect the function and growth of thyroid. However, there is little data on the effect of phthalates on thyroid oncogenesis. Here we explored the associations between phthalates exposure and the risks of thyroid cancer and benign nodule. We sex-matched 144 thyroid cancer, 138 benign nodule patients and 144 healthy adults from Wuhan, China. Eight phthalate metabolites in spot urine samples were quantified using high-performance liquid chromatography and tandem mass spectrometry. The associations of creatinine-corrected urinary phthalate metabolites with the risks of thyroid cancer and benign nodule were assessed using multivariable logistic regression models. We found that urinary monomethyl phthalate (MMP), mono(2-ethyl-5hydroxyhexyl) phthalate (MEHHP) and mono(2-ethylhexyl) phthalate (MEHP) associated with increased risks of thyroid cancer and nodule, with adjusted odds ratios (ORs) ranging from 1.74 to 4.78 comparing the extreme tertiles, and urinary monobutyl phthalate (MBP) was associated with decreased risks of thyroid cancer and benign nodule (all P for trends < 0.05). Male-specific positive associations of urinary monoethyl phthalate (MEP) with thyroid cancer and nodule as well as urinary mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) with thyroid cancer were also observed. Our results suggest that exposure to certain phthalates may contribute to increased risks of thyroid cancer and benign nodule.

Urinary levels of bisphenol A, F and S and markers of oxidative stress among healthy adult men: Variability and association analysis.

BACKGROUND: Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as alternatives to endocrine disrupting chemical bisphenol A (BPA). Evidence from in vitro and animal studies demonstrates that BPA, BPF and BPS induce oxidative stress, a proposed mechanism that is relevant to various adverse health effects. Evaluation in humans is hampered by the potentially high within-subject variability of urinary measurements. OBJECTIVE: To evaluate the variability and associations of levels of BPA, BPS, BPF and 3 oxidative stress markers [i.e., 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine collected on multiple occasions over 3 months. METHOD: A total of 529 spot urine samples, including 88 first morning voids (FMVs) and 24-h specimens, were gathered from 11 adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analyzed for BPA, BPF, BPS, 8-OHdG, 8-isoPGF2α and HNE-MA. Intraclass correlation coefficients (ICCs) were estimated to characterize the reproducibility of urinary bisphenols and oxidative stress markers, and linear mixed models were applied to assess the associations between markers of exposure and response. RESULTS: BPA and BPF were detected in ≥85% of the spot samples, while BPS in 13% of the samples. High degrees of within-subject variability were found for BPA, BPF, 8-OHdG, 8-isoPGF2α and HNE-MA in spot samples, FMVs and 24-h specimens (creatinine-corrected ICCs ≤ 0.37). The sensitivities were low-to-moderate (0.30-0.63) when using single spot samples or FMVs to predict high (>27th, or 36th percentile) 3-month average urinary levels of BPA, BPF, 8-OHdG, 8-isoPGF2α and HNE-MA. Collecting repeated specimens at different time points improved the accuracy of classification for markers of exposure and response. Elevated urinary BPA and BPF were associated with significantly higher levels of oxidative stress markers. CONCLUSIONS: Repeated urinary specimens are required to characterize bisphenol exposure levels and the oxidative stress status of individuals. Exposure to BPA and BPF may partly contribute to the elevated urinary levels of oxidative stress makers in adult men.

Effect modification of CPY2E1 and GSTZ1 genetic polymorphisms on associations between prenatal disinfection by-products exposure and birth outcomes.

BACKGROUND: Prenatal disinfection by-products (DBPs) exposure is linked with adverse birth outcomes. Genetic susceptibility to DBP metabolism may modify the exposure-outcome associations. OBJECT: To investigate whether CYP2E1 and GSTZ1 genetic polymorphisms modified the associations of prenatal DBP exposures with adverse birth outcomes. METHODS: Two biomarkers of DBP exposures including trihalomethanes (THMs) in blood and trichloroacetic acid (TCAA) in urine were determined among 426 pregnant women from a Chinese cohort study. CYP2E1 (rs2031920, rs3813867, and rs915906) and GSTZ1 (rs7975) polymorphisms in cord blood were genotyped. Statistical interactions between prenatal DBP exposures and newborns CYP2E1 and GSTZ1 polymorphisms on birth outcomes (birth weight, birth length, and gestational age) were examined by multivariable linear regression with adjustment for potential confounders. RESULTS: We found that newborns CYP2E1 genetic polymorphisms (rs2031920 and rs3813867) modified the associations of maternal blood THMs or urinary TCAA levels with birth outcomes. However, these interactions were nonsignificant after Bonferroni correction for multiple comparisons, except for the interaction between maternal blood BrTHMs [sum of dibromochloromethane (DBCM), bromodichloromethane (BDCM), and bromoform (TBM)] and newborns CYP2E1 gene rs2031920 polymorphisms on birth weight (P for interaction = 0.003). CONCLUSION: Newborns genetic variations of CYP2E1 rs2031920 may modify the impacts of prenatal BrTHM exposure on birth weight. This finding needs to be further confirmed.

[Pollution Characteristics and Emission Coefficients of Volatile Organic Compounds from the Packaging and Printing Industry in Zhejiang Province].

This paper presents the raw material composition and VOC treatment status of the packaging and printing industry in Zhejiang Province based on the survey data obtained in 2015 of 254 packaging and printing enterprises. To analyze the emission characteristics and calculate the emission coefficients of the packaging and printing industry, 100 typical enterprises were further screened according to different printing processes. The results showed that about two-thirds of packaging and printing enterprises failed to effectively dispose of VOCs; meanwhile, solvent-based materials were still commonly used in the packaging and printing industry. The main emission pollution factors of VOCs in the packaging and printing industry were ethyl acetate, isopropanol, ethanol, propyl acetate, and n-butyl acetate. The VOC emission coefficient of the packaging and printing industry in Zhejiang Province was 0.485 kg·kg-1, of which the gravure printing was the primary source with VOCs emission coefficient of 0.634 kg·kg-1. Compared with the material balance method, the error value from the emission coefficient method was less than 15%.

Prenatal phthalate exposure, birth outcomes and DNA methylation of Alu and LINE-1 repetitive elements: A pilot study in China.

BACKGROUND: Epigenetic mechanisms, such as altered DNA methylation, may participate in the relationship between prenatal phthalate exposure and adverse birth outcomes. OBJECTIVE: To explore the mediation effect of DNA methylation in the associations of phthalate exposure before delivery with birth outcomes in a Chinese cohort. METHODS: Eight phthalate metabolites in maternal urine before delivery and DNA methylation of Alu and long interspersed nucleotide elements (LINE-1) in cord blood were determined among 106 mother-infant pairs. General additive models were used to assess the associations of maternal urinary phthalate metabolites with birth outcomes and DNA methylation; the mediating role of DNA methylation in cord blood was evaluated by mediation analysis. RESULTS: We found sex-specific associations between prenatal phthalate exposure and birth outcomes and DNA methylation of cord blood. For example, the molar sum of di-2-(ethylhexyl) phthalate (∑DEHPm) metabolites in maternal urine was positively associated with gestational age among male newborns only (P < 0.05); maternal urinary monobenzyl phthalate (MBzP) was negatively associated with Alu methylation among female newborns only (P < 0.05). Mediation analysis did not find that methylation of Alu and LINE-1 to be a direct mediator in the relationships between maternal urinary phthalate metabolites before delivery and birth outcomes. CONCLUSION: Prenatal exposure to certain phthalates was associated with altered birth outcomes and decreased repetitive element methylation of newborns. However, the altered birth outcomes exerted by prenatal phthalate exposure does not seem to be directly mediated through repetitive element methylation in cord blood.

A solid composite microbial inoculant for the simultaneous removal of volatile organic sulfide compounds: Preparation, characterization, and its bioaugmentation of a biotrickling filter.

Volatile organic sulfide compounds (VOSCs) are usually resistant to biodegradation, thereby limiting the performance of traditional biotechnology dealing with waste gas containing such pollutants especially in mixture. In this study, a solid composite microbial inoculant (SCMI) was prepared to remove dimethyl sulfide (DMS) and propanethiol (PT). Given that the DMS degradation activity of Alcaligenes sp. SY1 is inducible and the PT-degradation activity of Pseudomonas putida S-1 is constitutive, different strategies are designed for cell cultivation to obtain high VOSC removal rates of SCMI. Compared with the microbial suspension, the prepared SCMI exhibited better storage stability at 4 and 25°C. Inoculation of the SCMI in biotrickling filters (BTFs) could effectively shorten the start-up period and enhance the removal performance. Microbial analysis by Illumina MiSeq indicated that Alcaligenes sp. SY1 and P. putida S-1 might be dominant and persistent among the microbial communities of the BTF during the operation.

[Removal of Volatile Sulfur Odor by the Biotrickling Filter].

The biodegradation of gas-phase mixtrue of dimethyl sulfide (DMS) and 1-propanethiol (PT) was examined in a biotrickling filter (BTF), inoculated with a microbial consortium composed of activated sewage sludge, and pure strains of Alcaligenes sp. SY1 and Pseudomonas putida. S-1. BTF could be successfully started up within only 11 days when the inlet concentrations of DMS and PT were both 50 mg·m-3 and EBRT was 30 s, with 90% removal efficiency (RE) of DMS and 100% RE of PT. In the steady state, the maximum elimination capacities of DMS and PT were 8.7 g·(m3·h)-1 and 12.4 g·(m3·h)-1, respectively. The presence of PT with a concentration up to 51 mg·m-3 showed an antagonistic removal pattern for DMS, but the opposite did not occur. Meanwhile, the BTF showed high efficiency in the biodegradation of H2S. When the concentration of H2S was as high as 230 mg·m-3, the RE of H2S could reach 98%. However, H2S showed a declining effect on the removal of DMS when the concentration exceeded 115 mg·m-3.

Induction of Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 During the Periovulatory Period in the Rat Ovary.

Ectonucleotide pyrophosphatase/phosphodiesterase 3 ( Enpp3) is involved in multiple physiological processes, such as morphological changes and inflammatory processes. The present study investigated the spatiotemporal expression pattern and regulatory mechanisms controlling expression of Enpp3 in the rat ovary during the periovulatory period. Immature female rats were injected with pregnant mare serum gonadotropin to stimulate follicular development. Ovaries, granulosa cells, or theca-interstitial cells were collected at various times after human chorionic gonadotropin (hCG) administration. Real-time polymerase chain reaction analysis revealed that messenger RNA (mRNA) for Enpp3 was highly induced in both granulosa cells and theca-interstitial cells by hCG. In situ hybridization analysis demonstrated that Enpp3 mRNA expression was induced in theca cells at 4 hours after hCG, and the expression remained elevated until 12 hours after hCG. The expression of Enpp3 mRNA was stimulated in granulosa cells at 8 hours and reached the highest expression at 12 hours. Localization of Enpp3 mRNA was observed in newly forming corpora lutea by in situ hybridization. The hCG-stimulated expression of Enpp3 mRNA was blocked by a protein kinase C inhibitor (GF109203) instead of the protein kinase A inhibitor (H89). Furthermore, Enpp3 induction is dependent on new protein synthesis. Inhibition of progesterone action did not alter Enpp3 mRNA expression, whereas inhibition of prostaglandin synthesis or the epidermal growth factor pathway diminished Enpp3 mRNA levels. In conclusion, our findings suggest that the induction of the Enpp3 mRNA may be important for the morphological changes and inflammatory response during ovulation and luteinization.

Expression and regulation of the differentiation regulators ERBB Receptor Feedback Inhibitor 1 (ERRFI1) and Interferon-related Developmental Regulator 1 (IFRD1) during the periovulatory period in the rat ovary.

The current study investigated the regulation and the spatiotemporal expression pattern of Errfi1 and Ifrd1, genex encoding factors that regulate differentiation and cessation of cell division, in the rat ovary during the periovulatory period. Immature female rats (22-23 days old) were injected with pregnant-mare serum gonadotropin to stimulate folliculogenesis, followed by human chorionic gonadotropin (hCG) to induce ovulation. Ovaries, granulosa cells, theca-interstitial cells, or cumulus oocyte complexes (COCs) were collected at various times after hCG administration (n = 3 per time point). Expression analysis revealed that Errfi1 and Ifrd1 were highly induced in the ovary, although their spatiotemporal expression differed: In situ hybridization analysis demonstrated that Errfi1 mRNA expression was initially induced in theca-interstitial cells at 4 and 8 hr after hCG, then transitioned to granulosa cells at 12 hr, and decreased in newly forming corpora lutea at 24 hr. Ifrd1 mRNA, on the other hand, was primarily induced in granulosa cells, and expression remained elevated in newly forming corpora lutea. Interestingly, Errfi1 and Ifrd1 were also expressed in the COC, suggesting a potential role in cumulus cell expansion or oocyte maturation. Inhibition of progesterone or prostaglandin synthesis reduced Errfi1 and Ifrd1 transcription, whereas inhibition of epidermal growth factor signaling inhibited only Errfi1 mRNA abundance. Down-regulation of both genes led to further suppression of progesterone. Our findings thus suggest that the stimulation of Errfi1 and Ifrd1 may be important for theca and granulosa cell differentiation and COC expansion. Mol. Reprod. Dev. 83: 714-723, 2016 © 2016 Wiley Periodicals, Inc.

CYP2C19 polymorphism and clinical outcomes among patients of different races treated with clopidogrel: A systematic review and meta-analysis.

Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease (CAD) treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention (PCI). The primary outcome of our interest was the recurrence of major adverse cardiovascular events (MACE) in those CAD patients. Firstly, we found that the distribution of reduced-function CYP2C19 allele varied between Westerners and Asians. Among Asians, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 42.5% and 10%, respectively. While among Westerners, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 25.5% and 2.4%, respectively. Secondly, the impact of CYP2C19 polymorphism on clinical outcomes of patients treated with clopidogrel varied with races. Among Asians, only 2 reduced-function CYP2C19 mutant allele carriers had the reduced effect of clopidogrel. And the reduced effect was significant only after the 30th day of treatment. While among Westerners, both 1 and 2 reduced-function CYP2C19 allele carriers had the reduced effect, and it mainly occurred within the first 30 days. Thirdly, the safety of clopidogrel was almost the same among races. Reduced-function allele non-carriers had higher risk for total bleeding but did not have higher risk for major bleeding. It is suggested that CYP2C19 polymorphism affects the efficacy of clopidogrel differently among Westerners and Asians.

Systematic confirmation study of GWAS-identified genetic variants for Kawasaki disease in a Chinese population.

Genome-wide association studies (GWASs) have identified multiple single nucleotide polymorphisms (SNPs) associated with Kawasaki disease (KD). In this study, we replicated the associations of 10 GWAS-identified SNPs with KD in a Han Chinese population. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression, and cumulative effect of non-risk genotypes were also performed. Although none of the SNPs reached the corrected significance level, 4 SNPs showed nominal associations with KD risk. Compared with their respective wild type counterparts, rs1801274 AG+GG genotypes and rs3818298 TC+CC genotypes were nominally associated with the reduced risk of KD (OR = 0.77, 95% CI = 0.59-0.99, P = 0.045; OR = 0.74, 95% CI = 0.56-0.98, P = 0.038). Meanwhile, rs1801274 GG genotype, rs2736340 CC genotype or rs4813003 TT genotype showed a reduced risk trend (OR = 0.57, 95% CI = 0.35-0.93, P = 0.024; OR = 0.46, 95% CI = 0.26-0.83, P = 0.010; OR = 0.64, 95% CI = 0.43-0.94, P = 0.022), compared with rs1801274 AG+AA genotypes, rs2736340 CT+TT genotypes or rs4813003 TC+CC genotypes, respectively. Furthermore, a cumulative effect was observed with the ORs being gradually decreased with the increasing accumulative number of non-risk genotypes (Ptrend<0.001). In conclusion, our study suggests that 4 GWAS-identified SNPs, rs2736340, rs4813003, rs3818298 and rs1801274, were nominally associated with KD risk in a Han Chinese population individually and jointly.

[Removal of Waste Gas Containing Mixed Chlorinated Hydrocarbons by the Biotrickling Filter].

An experimental investigation on purification of waste gas contaminated with a mixture of dichloromethane (DCM) and dichloroethane(1,2-DCA) was conducted in a biotrickling filter (BTF) inoculated with activated sludge of pharmaceuticals industry. Stable removal efficiency(RE) above 80% for DCM and above 75% for 1,2-DCA were achieved after 35 days, indicating that biofilm was developed. The best elimination capacity (EC) of DCM and 1,2-DCA were 13 g.(m3.h)-1 and 10 g.(m3.h)-1 respectively. And there was a linear relationship between the production of CO2 and mixed gas EC, the maximum mineralization rate of mixed gas stabled at 61. 2%. The interaction test indicated that DCM and 1,2-DCA would inhibit with each other. The changing of biomass of BTF during the operation process was also been studied.