Development of a targeted method for DNA adductome and its application as sensitive biomarkers of ambient air pollution exposure.

DNA adducts are widely recognized as biomarkers of exposure to environmental carcinogens and associated health effects in toxicological and epidemiological studies. This study presents a targeted and sensitive method for comprehensive DNA adductome analysis using ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS). The method was developed using calf thymus DNA, with careful optimization of mass spectrometric parameters, chromatographic separation conditions, and pretreatment methods. Ultimately, a targeted method was established for 41 DNA adducts, which showed good linearity (R2 ≥0.992), recovery (80.1-119.4 %), accuracy (81.3-117.8 %), and precision (relative standard deviation <14.2 %). The established method was employed to analyze DNA adducts in peripheral blood cells from pregnant women in Shanxi and Beijing. Up to 23 DNA adducts were successfully detected in samples of varying sizes. From 2 µg of maternal DNA samples, seven specific adducts were identified: 5-methyl-2'-deoxycytidine (5-MedC), 5-hydroxymethyl-2'-deoxycytidine (5-HmdC), N6-methyl-2'-deoxyadenosine (N6-MedA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 5-hydroxy-2'-deoxycytidine (5-OHdC), 1,N6-etheno-2'-deoxyadenosine (1,N6-εdA), and N2-methyl-2'-deoxyguanosine (N2-MedG). This study reveals that exposure to higher concentrations of ambient air pollutants may elevate the levels of DNA methylation and oxidative damage at different base sites, highlighting the application potential of DNA adducts as sensitive biomarkers of air pollution exposure.

Cardiovascular effects of wearing respirators against particulate matter: A randomized crossover trial.

Fine particles (PM2.5) are implicated as an important risk to cardiovascular health. N95 respirators had been widely used to provide protection by filtering particles. Yet the practical effects of wearing respirators have not been fully understood. This study aimed to evaluate the cardiovascular effects of respirator wearing against PM2.5 and underpin the understanding of the mechanisms of cardiovascular responses triggered by PM2.5. We conducted a randomized, double-blind crossover trial among 52 healthy adults in Beijing, China. Participants were exposed to outdoor PM2.5 for 2 h in alterations wearing true respirators (with membranes) or sham ones (without membranes). We measured ambient PM2.5 and tested the filtration efficiency of the respirators. We compared the heart rate variability (HRV), blood pressure and arterial stiffness indicators between the true respirator group and the sham respirator group. Concentrations of ambient PM2.5 during the 2-h exposure ranged from 4.9 to 255.0 µg/m3. The filtration efficiency of true respirators was 90.1 % and that of sham ones was 18.7 %. Between-group differences varied by pollution levels. On less polluted days (PM2.5< 75 µg/m3), participants wearing true respirators showed lower levels of HRV and higher levels of heart rate compared with those wearing sham respirators. These between-group differences were inconspicuous on heavily polluted days (PM2.5≥ 75 µg/m3). We found that a 10 µg/m3 increase in PM2.5 was associated with a 2.2 % to 6.4 % decrease in HRV, prominent at 1 h after the start of exposure. N95 respirators have good performance in reducing PM2.5 exposure. Short-term exposure to PM2.5 can induce very acute responses in autonomic nervous function. However, the overall effects of wearing respirators might be not always favorable to human health in terms of their inherent adverse effects, which seem dependent on the levels of air pollution. Precise individual protection recommendations warrant to be developed.

Associations of maternal exposure to 41 metals/metalloids during early pregnancy with the risk of spontaneous preterm birth: Does oxidative stress or DNA methylation play a crucial role?

BACKGROUND: Few studies have explored the effects of multiple types of metals/metalloids on spontaneous preterm birth (SPB). A nested case-control study was conducted in Shanxi Province to investigate the associations between maternal exposure to 41 metals/metalloids during early pregnancy and the risk of SPB, and to clarify the underlying mechanisms of oxidative stress and DNA methylation. METHODS: A total of 74 controls with full-term delivery and 74 cases with SPB were included in the nested case-control study. The metals/metalloids in serum and the DNA adducts in peripheral blood cell DNA were determined using ICP-MS and UPLC-QqQ-MS/MS, respectively. Unconditional logistic regression models were employed to estimate the associations of the risk of SPB with the metal concentrations, as well as with the levels of oxidative stress/DNA methylation. In addition, linear regression models were used to investigate the associations between the metal/metalloid concentrations and the levels of oxidative stress/DNA methylation. RESULTS: After adjusting for potential confounders, the concentrations of Mn, Fe, Cu, Nd, Hg, and Pb in maternal serum during early pregnancy were positively associated with the risk of SPB. Compared with the lowest levels (Quartile 1) of Mn, Fe, Cu, Nd, Hg, and Pb, the odds ratios of SPB increased to 5.21 (95% CI: 1.63, 16.68), 3.47 (95% CI: 1.07, 11.21), 16.23 (95% CI: 3.86, 68.18), 10.54 (95% CI: 2.79, 39.86), 5.88 (95% CI: 1.72, 20.11), and 4.09 (95% CI: 1.31, 12.77) in the highest levels (Quartile 4), respectively. A significant increase in 8-OHdG was associated with the increased exposure to Fe, Pr, Eu, Er, and Lu. The levels of 5-MdC, 5-HmdC, and N6-MdA-the indicators of DNA methylation-were associated with exposure to multiple metals/metalloids. However, no significant associations were observed between the levels of oxidative stress or DNA methylation and the risk of SPB. CONCLUSIONS: Exposure to multiple types of metals/metalloids during early pregnancy is positively associated with the risk of SPB. Oxidative stress and DNA methylation are significantly associated with exposure to multiple metals/metalloids. Systemic oxidative stress and DNA methylation have not been proven to be the mediating mechanisms of metals increasing the risk of SPB.

The health effects of wearing facemasks on cardiopulmonary system of healthy young adults: A double-blinded, randomized crossover trial.

BACKGROUND: Facemask had increasingly been utilized as a personal protective measure to reduce exposure to ambient particulate matter (PM) during heavily-polluted days and routine life. However, evidence on the potential effects on cardiovascular system by wearing particulate-filtering facemask was limited. METHODS: We conducted a double-blinded randomized crossover trial (RCT) to evaluate the effects of wearing N95 facemasks on the molecular responses of cardiopulmonary system among 52 healthy college students in Beijing, China. We measured cardiopulmonary health indicators and collected biological samples before and after (up to 5 h at multiple time points) a 2-h walk to examine the changes in lung function, biomarkers of respiratory and systemic oxidative stress/inflammation. We applied linear mixed-effect models to evaluate the effect of the facemask-intervention on the health of cardio-pulmonary system. RESULTS: In the trial wearing real facemasks, FEV1 increased by 2.05% (95% CI: 0.27%-3.87%), 2.80% (95% CI: 1.00%-4.63%), and 2.87% (95% CI: 1.07%-4.70%) at V1 (30-min), V2 (3-h), and V3 (5-h) after the 2-h walk outsides, respectively. Compared with participants wearing the sham mask, the percentage change of nitrate in EBC was lower among those wearing the real mask. After the 2-h exposure, urinary MDA levels increased compared to the baseline in both trials. Real trial was lower than sham trial for 6 cytokines (i.e., IL-6, IL-10, IL-13, IL-17A, IFN-γ and TNF-α) in serum at 5-h post-exposure. Wearing facemasks on polluted days produced better improvement, however, on cleaner days, the improvement was weaker. CONCLUSIONS: Short-term use of N95 facemasks appeared to effectively reduce the levels of lung function declines, the respiratory oxidative stress, and the systemic inflammation/oxidative stress which may be induced by short-term exposure to PM. Wearing facemasks on polluted days (PM2.5 > 75 µg/m3) presented larger beneficial effects on the cardiopulmonary health than in clean days (PM2.5 < 75 µg/m3).

Enhanced biodegradation of chlorobenzene via combined Fe3+ and Zn2+ based on rhamnolipid solubilisation.

Biotrickling filters (BTFs) for hydrophobic chlorobenzene (CB) purification are limited by mass transfer and biodegradation. The CB mass transfer rate could be improved by 150 mg/L rhamnolipids. This study evaluated the combined use of Fe3+ and Zn2+ to enhance biodegradation in a BTF over 35 day. The effects of these trace elements were analysed under different inlet concentrations (250, 600, 900, and 1200 mg/L) and empty bed residence times (EBRTs; 60, 45, and 32 sec). Batch experiments showed that the promoting effects of Fe3+/Zn2+ on microbial growth and metabolism were highest for 3 mg/L Fe3+ and 2 mg/L Zn2+, followed by 2 mg/L Zn2+, and lowest at 3 mg/L Fe3+. Compared to BTF in the absence of Fe3+ and Zn2+, the average CB elimination capacity and removal efficiency in the presence of Fe3+ and Zn2+ increased from 61.54 to 65.79 g/(m3⋅hr) and from 80.93% to 89.37%, respectively, at an EBRT of 60 sec. The average removal efficiency at EBRTs of 60, 45, and 32 sec increased by 2.89%, 5.63%, and 11.61%, respectively. The chemical composition (proteins (PN), polysaccharides (PS)) and functional groups of the biofilm were analysed at 60, 81, and 95 day. Fe3+ and Zn2+ significantly enhanced PN and PS secretion, which may have promoted CB adsorption and biodegradation. High-throughput sequencing revealed the promoting effect of Fe3+ and Zn2+ on bacterial populations. The combination of Fe3+ and Zn2+ with rhamnolipids was an efficient method for improving CB biodegradation in BTFs.

Sludge amendment accelerating reclamation process of reconstructed mining substrates.

We constructed a mining soil restoration system combining plant, complex substrate and microbe. Sludge was added to reconstructed mine substrates (RMS) to accelerate the reclamation process. The effect of sludge on plant growth, microbial activity, soil aggregate stability, and aggregation-associated soil characteristics was monitored during 10 years of reclamation. Results show that the height and total biomass of ryegrass increases with reclamation time. Sludge amendment increases the aggregate binding agent content and soil aggregate stability. Soil organic carbon (SOC) and light-fraction SOC (LFOC) in the RMS increase by 151% and 247% compared with those of the control, respectively. A similar trend was observed for the glomalin-related soil protein (GRSP). Stable soil aggregate indexes increase until the seventh year. In short, the variables of RMS determined after 3-7 years insignificantly differ from those of the untreated sample in the tenth-year. Furthermore, significant positive correlations between the GRSP and SOC and GRSP and soil structure-related variables were observed in RMS. Biological stimulation of the SOC and GRSP accelerates the recovery of the soil structure and ecosystem function. Consequently, the plant-complex substrate-microbe ecological restoration system can be used as an effective tool in early mining soil reclamation.

Monitoring DNA adducts in human blood samples using magnetic Fe3O4@graphene oxide as a nano-adsorbent and mass spectrometry.

DNA adducts usually occur at a level of 0.1-1 adducts per 108 unmodified DNA bases, which can cause many adverse health effects if not normally repaired. Using microgram amounts of DNA to detect DNA adducts remains challenging due to the extremely low levels. Commercial solid phase extraction is the most widely used method for extracting DNA adducts from biological samples, but it is time consuming and costly, and the hydrophobic interactions between various alkyl-bonded phases and analytes typically lack selectivity when used to extract DNA adducts. Therefore, an effective method for DNA adducts analysis based on Fe3O4@graphene oxide (GO) nano-adsorbent and ultra-performance liquid chromatography-triple quadrupole mass spectrometry detection was developed in this study, in which the selectivity may also be increased by π-π stacking interactions between GO and adduct molecules. Several variables, including the extraction time, extraction pH, nano-sorbent amount and elution solvent were optimized, to achieve the best extraction efficiency using the proposed method. A small amount of Fe3O4@GO (2.5 mg) exhibited a good adsorption performance for the model DNA adducts, and butanol containing 4% NH3·H2O showed good elution effects. Under the optimized conditions, satisfying recoveries (78-107%) from calf thymus DNA samples were achieved, and 2 adducts were detected in only 2 µg of blood DNA. This method can be used as an effective strategy for DNA adduct analysis, and can be extended to other biological samples.

The styrene purification performance of biotrickling filter with toluene-styrene acclimatization under acidic conditions.

The obvious disadvantages of biotrickling filters (BTFs) are the long start-up time and low removal efficiency (RE) when treating refractory hydrophobic volatile organic compounds (VOCs), which limits its industrial application. It is worthwhile to investigate how to reduce the start-up period of the BTF for treating hydrophobic VOCs. Here, we present the first study to evaluate the strategy of toluene induction combined with toluene-styrene synchronous acclimatization during start-up in a laboratory-scale BTF inoculated with activated sludge for styrene removal, as well as the effects of styrene inlet concentration (0.279 to 2.659 g·m-3), empty bed residence time (EBRT) (i.e., 136, 90, 68, 45, 34 sec), humidity (7.7% to 88.9%), and pH (i.e., 4, 3, 2.5, 2) on the performance of the BTF system. The experiments were carried out under acidic conditions (pH 4.5) to make fungi dominant in the BTF. The start-up period for styrene in the BTF was shortened to about 28 days. A maximum elimination capacity (ECmax) of 126 g·m-3·hr-1 with an RE of 80% was attained when styrene inlet loading rate (ILR) was below 180 g·m-3·hr-1. The highest styrene RE(s) [of BTF] that could be achieved were 95% and 93.4%, respectively, for humidity of 7.7% and at pH 2. A single dominant fungal strain was isolated and identified as Candida palmioleophila strain MA-M11 based on the 26S ribosomal RNA gene. Overall, the styrene induction with the toluene-styrene synchronous acclimatization could markedly reduce the start-up period and enhance the RE of styrene. The BTF dominated by fungi exhibited good performance under low pH and humidity and great potential in treating styrene with higher inlet concentrations. Implications: The application of the toluene induction combined with toluene-styrene synchronous acclimatization demonstrated to be a promising approach for the highly efficient removal of styrene. The toluene induction can accelerate biofilm formation, and the adaptability of microorganisms to styrene can be improved rapidly by the toluene-styrene synchronous acclimatization. The integrated application of two technologies can shorten the start-up period of biotrickling filters markedly and promote its industrial application.

Nonionic surfactant enhanced biodegradation of m-xylene by mixed bacteria and its application in biotrickling filter.

In this study, m-xylene biodegradation was examined in bacteria-water mixed solution and biotrickling filter (BTF) systems amended with the nonionic surfactant Tween 80. The mixed bacteria were obtained from the activated sludge of a coking plant through a multisubstrate acclimatization process. High-throughput sequencing analysis revealed that Rhodanobacter sp. was the dominant species among the mixed bacteria. In the bacteria-water mixed solution, the bacterial density increased with increasing Tween 80 concentration. Hence, Tween 80 could be utilized as substrate by the mixed bacteria. Tween 80, with concentrations of 50-100 mg L-1, could enhance the bioavailability of m-xylene and consequently improve the degradation efficiency of m-xylene. However, further increasing the initial concentration of Tween 80 would decrease the degradation efficiency of m-xylene. At concentrations exceeding 100 mg L-1, Tween 80 was preferentially degraded by the mixed bacteria over m-xylene. In BTF systems, when the m-xylene inlet concentration was 1200 mg m-3 and the empty bed residence time was 20 sec, the removal efficiency and elimination capacity of BTF1 with Tween 80 addition were at most 20% and 24% higher than those of BTF2 without Tween 80 addition. Overall, the integrated application of the mixed bacteria and surfactant was demonstrated to be a highly effective strategy for m-xylene waste gas treatment. IMPLICATIONS: The integrated application of mixed bacteria and surfactant was demonstrated to be a promising approach for the highly efficient removal of m-xylene. Surfactant can activate mixed bacteria to degrade m-xylene by increasing its bioavailability. Besides, surfactant can be utilized as carbon source by the mixed bacteria so that the growth of mixed bacteria can be promoted. It is expected that the integrated application of both technologies will become more common in future chemical industry.

Surfactant-enhanced biodegradation of crude oil by mixed bacterial consortium in contaminated soil.

This study evaluated the effects of two surfactants (i.e., Tween 80 and SDS) on biodegradation of crude oil by mixed bacterial consortium in soil-aqueous system. The mixed bacterial consortium was domesticated from the activated sludge of cooking plant through a progressive domestication process. High-throughput sequencing analysis revealed that Rhodanobacter sp. was the dominant bacteria. The higher CMCeff value for two surfactants was observed in soil-aqueous system compared with that in aqueous system, which was likely due to their adsorption onto soil particles. Either Tween 80 or SDS can be utilized as carbon source and promote the growth of mixed bacterial consortium. Further findings evidenced that the degradation of crude oil can be enhanced by adding either Tween 80 or SDS. The performance of Tween 80 was generally superior to SDS for the crude oil degradation. The highest crude oil degradation efficiency was 42.2 and 31.0% under the conditions of 5 CMCeff of Tween 80 and 2 CMCeff of SDS, respectively. Furthermore, the degradation efficiency of crude oil in remediation experiment (i.e., 77%) evidenced that the integration of adding Tween 80 and inoculating mixed bacterial consortium was effective for crude oil-contaminated soil decontamination.

[HIV resistance in men who have sex with men: a Meta-analysis].

OBJECTIVE: To assess the prevalence of HIV primary drug resistance and drug resistance gene mutations among men who have sex with men (MSM).
 Methods: We searched eight electronic databases (CNKI, VIP, CBM, Wanfang Database, PubMed, Web of Knowledge, Springer, Medline) for the studies of HIV drug resistance relevant to MSM. Drug resistance and drug resistance mutations data were pooled and analyzed according to statistical test of homogeneity. Subgroups were further divided according to sample size, location, race, quality rating score, sampling time.
 Results: Forty-three studies were included in this Meta-analysis. The pooled rate of total to protease inhibitor (PI), nucleoside reverse transcriptase inhibitor(NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) were 10.21% (95% CI 8.65% to12.03%), 2.98% (95% CI 2.25% to 3.93%), 4.05% (95% CI 3.14% to 5.21%), 4.42% (95% CI 3.31% to 5.88%), respectively. The pooled rates of PI major mutation, PI secondary mutations, NRTI mutations and NNRTI mutations were 0.55% (95% CI 0.38% to 0.80%), 1.31% (95% CI 0.98% to 1.75%), 0.85% (95% CI 0.51% to 1.40%), 1.19% (95% CI 0.70% to 2.01%), 0.79% (95% CI 0.55% to 1.13%), 1.73% (95% CI 1.21% to 2.46%), 0.86% (95% CI 0.61% to 1.21%), 2.24% (95% CI 1.77% to 2.83%), respectively. Sample size, region, and race were heterogeneous sources; the rate of resistance mutations and gene mutation rate were different in different subgroups.
 Conclusion: The prevalence of primary drug resistance among MSM was high in Americas and Europe, and it was gradually increased in Asia. We should pay attention to the high incidence of PI secondary mutations.

Prevalence of HIV and syphilis co-infection and associated factors among non-commercial men who have sex with men attending a sexually transmitted disease clinic in Shenzhen, China.

BACKGROUND: Although HIV and syphilis co-infection has been frequently observed in men who have sex with men (MSM), only few studies have focused on it. Different subgroups of MSM might exhibit heterogeneous HIV and syphilis risk profiles, indicating that interventions for HIV and HIV-related co-infections may vary with different subgroups of MSM. However, no previous study has investigated HIV and syphilis co-infection among non-commercial MSM (ncMSM) attending a sexually transmitted disease (STD) clinic. Therefore, this study aimed to explore the prevalence of HIV and syphilis co-infection and associated factors among ncMSM attending an STD clinic in Shenzhen, China. METHODS: NcMSM attending the STD clinic of Shenzhen Center for Chronic Disease Control were recruited in this cross-sectional study every Monday between March 2013 and August 2015 using a site based convenience sampling method. An anonymous questionnaire was used to collect data regarding socio-demographic characteristics, risky sexual behaviors and HIV-related knowledge. Blood samples were collected to perform HIV and syphilis tests. RESULTS: Totally 533 participants were enrolled in this study and the prevalence of HIV and syphilis co-infection among them was 13.13%. Multivariable analyses indicated that having lived in Shenzhen for less than one year (aOR = 2.80, 95% CI = 1.30-6.05), having first anal sexual intercourse before the age of 18 (aOR = 2.78, 95% CI = 1.29-5.89), having 3 to 5 anal sexual partners in the past six months (aOR = 2.54, 95% CI = 1.19-5.40), playing exclusively receptive (aOR = 6.87, 95% CI = 3.02-15.61) or both insertive and receptive (aOR = 3.65, 95% CI = 1.64-8.09) roles in anal sexual intercourse and not always using condom in anal sexual intercourse (aOR = 2.13, 95% CI = 1.08-4.19) were associated risk factors for HIV and syphilis co-infection, relative to the non-infected ncMSM. Compared with the mono-infected ncMSM, associated risk factors for the co-infection were being unmarried (aOR = 2.47, 95% CI = 1.03-5.89) and playing exclusively receptive role (aOR = 2.44, 95% CI = 1.04-5.73) in anal sexual intercourse. CONCLUSIONS: HIV and syphilis co-infection is quite prevalent among the study participants in Shenzhen. Integrated and intensified intervention strategies, specifically targeting at the non-infected and mono-infected ncMSM attending the STD clinic, are needed to reduce HIV and syphilis co-infection. Most importantly, non-infected and mono-infected ncMSM attending the STD clinic with the aforementioned associated risk factors should be given special concern.

Early Sexual Debut and HIV Infection among Men Who Have Sex with Men in Shenzhen, China.

Studies investigating the association between early sexual debut and human immunodeficiency virus (HIV) infection have mainly focused on Africans or females but rarely on men who have sex with men (MSM) in China. This study, therefore, mainly aimed at exploring the association between early sexual debut and HIV infection among MSM in Shenzhen, China. A total of 533 MSM were enrolled in this study using a convenience sampling method. Information about sociodemographic characteristics and risky sexual behaviors was collected. It was found that the prevalence of HIV infection was 24.2% among this study population and 66.4% of the MSM reported having had vaginal sexual intercourse with females. The mean ages at first vaginal sexual intercourse, first anal sexual intercourse, and first sexual intercourse were 21.38, 22.43, and 19.87 years, respectively. Multivariable logistic regression analyses showed that the MSM who experienced early anal sexual debut were more likely to be infected with HIV than those who did not. The results indicate that HIV infection is quite prevalent among MSM in Shenzhen. Early and efficient intervention strategies should be taken, and the MSM experiencing early anal sexual debut should be given special attention.

[Research progress on molecular genetics of male homosexuality].

Sexual orientation is influenced by both environmental factors and biological factors. Family and twin studies have shown that genetic factors play an important role in the formation of male homosexuality. Genome-wide scan also revealed candidate chromosomal regions which may be associated with male homosexuality, but so far no clearly related genes have been found. This article reviews the progress of relevant studies and candidate genes which are related to male homosexuality.

Analysis of the Association between Catechol-O-Methyltransferase Val158Met and Male Sexual Orientation.

INTRODUCTION: Male sexual orientation is thought to have a genetic component. However, previous studies have failed to generate positive results from among candidate genes. Catechol-O-methyltransferase (COMT), located on chromosome 22, has six exons, spans 27 kb, and encodes a protein of 271 amino acids. COMT has an important role in regulating the embryonic levels of catecholamine neurotransmitters (such as dopamine, norepinephrine, and epinephrine) and estrogens. COMT is also thought to be related to sexual orientation. AIMS: This study aimed to investigate the relationship between the COMT Val158Met variant and male sexual orientation. We performed association analysis of the COMT gene single nucleotide polymorphism, Val158Met, in 409 homosexual cases and 387 heterosexual control Chinese men. COMT polymorphism status was determined using a polymerase chain reaction-based assay. METHODS: Polymerase chain reaction was performed to genotype the COMT Val158Met polymorphism. MAIN OUTCOME MEASURES: The frequency differences of the genotype and alleles distribution between the male homosexual and control groups. RESULTS: Significant differences, both in genotype and alleles, between male homosexual individuals and controls indicated a genetic component related to male homosexuality. The Val allele recessive model could be an interrelated genetic model of the cause of male homosexuality. CONCLUSION: The COMT Val158Met variant might be associated with male sexual orientation and a recessive model was suggested.

Prognostic Value of Yes-Associated Protein 1 (YAP1) in Various Cancers: A Meta-Analysis.

BACKGROUND: Yes-associated protein 1 (YAP1) is an effector of Hippo pathway, which is critical for regulating organ size, cell proliferation and tumor growth in mammals. Many previous studies have explored the relationship between YAP1 and various types of cancer. However, these studies were limited by the small samples size and the findings were inconsistent among them. Therefore, a meta-analysis was conducted to assess the association between YAP1 and malignancies. METHODS: A systematic literature search was conducted for eligible studies in the PubMed, Corchane Library, Web of Knowledge, EMBASE and CBM disc databases from inception to August 1st 2014. After heterogeneity analysis, pooled harzad ratio (HR) with 95% confidence interval (95%CI) using both fixed and random effect models were estimated in STATA 10.0. Meta regression analysis, subgroup analysis and sensitivity analysis were performed to explore the potential sources of heterogeneity and to evaluate the robustness of the result. Publication bias was assessed by Egger's test and funnel plot. RESULTS: A total of 21 unique articles from 2009 to 2014, comprising 2983 patients, were analyzed in the meta-analysis. The association of YAP1 expression and overall survival time (OS) was evaluated in 20 studies including 2067 patients. Positive YAP1 showed poorer OS (HR = 1.826; 95% CI = 1.465-2.275; p <0.002). For evaluating disease-free survival time (DFS), 10 studies with 1139 patients were analyzed. Positive YAP1 indicated worse DFS (HR = 2.114; 95%CI = 1.406-3.179; p <0.001). Subgroup analysis showed that both positive nuclear YAP1 (HR = 1.390, 95% CI: 0.810-2.400, p = 0.729) and up-regulation overall YAP1 (HR = 2.237, 95% CI: 1.548-3.232, p <0.001) had poorer OS for patients with malignancies. Similarly, both positive nuclear YAP1 (HR = 3.733, 95% CI: 1.469-9.483, p = 0.001) and up-regulation overall YAP1 (HR = 1.481, 95% CI: 1.163-1.886, p = 0.554) showed worse DFS. The patients with urogenital system cancer had the poorest OS (HR = 2.133, 95% CI: 1.549-2.937, p = 0.020). The patients with alimentary system cancer had the most significant impact on DFS (HR = 1.879, 95% CI: 1.537-2.297, p <0.001). CONCLUSION: Both overall and nuclear YAP1 overexpression are intimately associated with adverse OS and DFS in numerous cancers, suggesting that YAP1 may act as a potential therapeutic targets of these malignancies in the future.

Clinical significance of mismatch repair gene expression in sporadic colorectal cancer.

Mismatch repair (MMR) genes play an important role in the occurrence and development of sporadic colorectal cancer; however, the effect of MMR genes on clinicopathological features and prognosis remains unclear. The aim of the present study was to observe the clinical significance of MMR gene expression in sporadic colorectal cancer. Clinicopathological data and postoperative samples from 404 patients with sporadic colorectal cancer were obtained from the Affiliated Tumor Hospital of Xinjiang Medical University. The immunohistochemistry PV-9000 two-step method was performed to measure the protein expression of human mutL homolog 1 (hMLH1), human mutS homolog (hMSH) 2, human postmeiotic segregation increased 2 (hPSM2) and hMSH6. Differences in clinicopathological features, family history and survival time subsequent to surgery between groups with normal and aberrant MMR protein (MMRP) expression were compared. A total of 27.23% of all patients showed aberrant nuclear staining of MMRP. Among the patients with aberrant MMRP expression, a higher proportion of patients showed aberrant expression of more than one type of MMRP than aberrant expression of only one type of MMRP. Aberrant expression of hMLH1/hPSM2 was most commonly observed (29/404). In addition, aberrant MMRP expression in colorectal cancer was indicated predominantly in the right hemicolon. Histological type primarily showed mucinous adenocarcinoma. In addition, with increasing body mass index (BMI), the MMRP deficiency rate was also shown to increase gradually. There was a close association between MMRP expression deficiency and family history of cancer (P<0.05). For TNM stage III patients, the Kaplan-Meier survival curve showed that the aberrant MMRP expression group had a three-year disease-free survival (DFS) rate of 66.67%, which was longer than the DFS rate of the normal group (55.41%), with no statistical difference (P>0.05). In conclusion, the immunohistochemistry PV-9000 two-step method can be used to measure MMRP expression in colorectal cancer. Aberrant MMRP expression is closely correlated with tumor location, histological type, BMI and tumor family history in sporadic colorectal cancer. Aberrant MMRP expression may have an effect on the prognosis of stage III patients.

Prognostic significance of preoperative fibrinogen in patients with colon cancer.

AIM: To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients. METHODS: A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1(st) 2005 to June 1(st) 2008 were enrolled in the study. All patients received radical surgery as their primary treatment method. Preoperative fibrinogen was detected by the Clauss method, and all patients were followed up after surgery. Preoperative fibrinogen measurements were correlated with a number of clinicopathological parameters using the Student t test and analysis of variance. Survival analyses were performed by the Kaplan-Meier method and Cox regression modeling to measure 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: The mean preoperative fibrinogen concentration of all colon cancer patients was 3.17 ± 0.88 g/L. Statistically significant differences were found between preoperative fibrinogen levels and the clinicopathological parameters of age, smoking status, tumor size, tumor location, tumor-node-metastasis (TNM) stage, modified Glasgow prognostic scores (mGPS), white blood cell (WBC) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) levels. Univariate survival analysis showed that TNM stage, tumor cell differentiation grade, vascular invasion, mGPS score, preoperative fibrinogen, WBC, NLR, PLR and CEA all correlated with both OS and DFS. Alpha-fetoprotein (AFP) and body mass index correlated only with OS. Kaplan-Meier analysis revealed that both OS and DFS of the total cohort, as well as of the stage II and III patients, were higher in the hypofibrinogen group compared to the hyperfibrinogen group (all P < 0.05). In contrast, there was no significant difference between OS and DFS in stage I patients with low or high fibrinogen levels. Cox regression analysis indicated preoperative fibrinogen levels, TNM stage, mGPS score, CEA, and AFP levels correlated with both OS and DFS. CONCLUSION: Preoperative fibrinogen levels can serve as an independent prognostic marker to evaluate patient response to colon cancer treatment.

Genetic effects have a dominant role on poor responses to infant vaccination to hepatitis B virus.

The objective of this study was to investigate the overall contribution of genetic and environmental effects on poor response to hepatitis B virus (HBV) vaccination in Chinese infants. One-year-old healthy twins were recruited from child-care settings. Parental factors, neonates' condition at birth, postnatal infant feeding history and growth measurements during the 12 months were investigated by conducting an interview and checking the medical records. HBV-related markers were examined at 1 year of age. Heritability of surface antibody to HBV (anti-HBs) concentrations (ordinal variable) among twins was estimated using MX software. The role of perinatal environmental factors on poor vaccine response (anti-HBs<100 mIU ml(-1)) was analyzed using XTGEE (fit population-averaged panel-data models by using GEE) programs. Overall, 172 out of 225 recruited twin pairs were analyzed for heritability, including 82 pairs (47.67%) of monozygotic twins and 90 pairs of dizygotic twins, which consisted 43 pairs of (25.0%) opposite sex twins, 29 pairs of male twins and 18 pairs of female twins. Seventy-one (19.9%) of 370 twins showed poor responses to HBV vaccine. An additive genetic (0.91 of the variance)-random environmental (0.09 of the variance)-model best fit the variation of anti-HBs response. Risk factor analysis showed that with a smoking father and low birth weight, the infants were associated with an increased risk of poor response to HBV vaccination (odds ratio (OR)=4.50, 95% confidence interval (CI): 2.52-8.03 and OR=2.55, 95% CI: 1.33-4.87, respectively). Higher Apgar score and gaining more body weight in the first year of life reduced this risk. Genetic factors have a dominant role in determining infant HBV vaccination responses (91%) compared with perinatal environmental factors.