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Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.
Maternal one-carbon metabolism during pregnancy is crucial for fetal development and programming by DNA methylation. However, evidence on one-carbon biomarkers other than folate is lacking. We, therefore, investigated whether maternal plasma methyl donors, that is, choline, betaine and methionine, are associated with birth outcomes. Blood samples were obtained from 115 women during gestation (median 26·3 weeks, 90 % range 22·7–33·0 weeks). Plasma choline, betaine, methionine and dimethylglycine were measured using HPLC-tandem MS. Multivariate linear and logistic regression models were used to estimate the association between plasma biomarkers and birth weight, birth length, the risk of small-for-gestational-age and large-for-gestational-age (LGA). Higher level of maternal betaine was associated with lower birth weight (–130·3 (95 % CI –244·8, –15·9) per 1 sd increment for log-transformed betaine). Higher maternal methionine was associated with lower risk of LGA, and adjusted OR, with 95 % CI for 1 sd increase in methionine concentration was 0·44 (95 % CI 0·21, 0·89). Stratified analyses according to infant sex or maternal plasma homocysteine status showed that reduction in birth weight in relation to maternal betaine was only limited to male infants or to who had higher maternal homocysteine status (≥5·1 µmol/l). Higher maternal betaine status was associated with reduced birth weight. Maternal methionine was inversely associated with LGA risk. These findings are needed to be replicated in future larger studies.
This study aimed to reveal the associated risk factors for latent tuberculosis infection (LTBI) detected by T-SPOT.TB assay among health care workers (HCWs) at different working locations or job categories in China. This cross-sectional study included 934 HCWs who underwent the T-SPOT.TB assay. Demographic and social characteristics of the participants, including age, sex, job categories, department/ward and duration of healthcare service, were recorded. Among 934 HCWs, 267 (28.5867%) were diagnosed as having LTBI with positive T-SPOT.TB assay. HCWs working in inpatient tuberculosis (TB) (odds ratio (OR) 2.917; 95% confidence interval (CI) 1.852–4.596; P < 0.001) and respiratory wards (OR 1.840; 95% CI 1.124–3.011; P = 0.015), and with longer duration of healthcare service (OR 1.048; 95% CI 1.016–1.080; P = 0.003) were risk factors for positive T-SPOT.TB result. Furthermore, longer working duration increased the positive rate of T-SPOT.TB results for physicians and nurses, and physicians had higher risks than nurses for the same working duration. Inpatient TB and respiratory wards were high-risk working locations for HCWs with LTBI, and longer duration of healthcare service also increased the risk of LTBI among HCWs. A complete strategy for TB infection control and protection awareness among HCWs should be enhanced.
Trypophloeus klimeschi Eggers (Coleoptera: Curculionidae: Scolytinae) was first discovered in China in 2003, and it exhibits strong species specificity to Populus alba var. pyramidalis Bunge (Salicaceae). To screen plant volatile compounds for monitoring and trapping T. klimeschi, the electroantennogram responses of adult T. klimeschi to eight plant volatiles, including nonanal, 2-methylbutanal, decanal, 2-hydroxybenzaldehyde, (Z)-3-hexen-1-ol benzoate, methyl benzoate, methyl salicylate, and geraniol were tested at various concentrations. Behavioural responses of female and male adults to various concentrations of these eight plant volatiles were also determined using a Y-tube olfactometer. We then tested the effectiveness of these compounds as lures for trapping T. klimeschi in the field. Electroantennogram tests showed that T. klimeschi possesses olfactory sensitivity for eight compounds. Additionally, walking T. klimeschi exhibited attraction to low concentrations (≤ 1 μg/μL) of all eight compounds in Y-tube olfactometer. Field experiment results indicated that baits composed of each volatile compound alone were more attractive to greater numbers of T. klimeschi than the control. The methyl benzoate bait was better attracted by T. klimeschi than other tested volatiles. These results suggest that these compounds could be used in attraction of this stem-boring pest. This study could have important implications for the development of an effective semiochemical-based management tool for T. klimeschi in the field.
Seed reserves play vital roles in seed germination and seedling growth and their variation may be related to various environment factors, plant traits and phylogenetic history. Here, the evolutionary correlation associated with seed mass and altitude and carbon (C), nitrogen (N) and phosphorus (P) allocation of seeds among 253 alpine herbaceous plants was tested. In this study, phylogeny had strong limitations on nutrient allocation of seeds across species, and species from younger phylogenetic groups tended to have higher N and P contents, which might be considered as the evolutionary selection of seed plants. Higher seed N and P content would help seedlings to gain more survival chance and stronger competitive capacity, and their progeny would be more likely to be preserved. When phylogeny was considered, altitude only had a significant positive effect on P content, but the negative effects on seed mass were all expressed. The independent effects of altitude and seed mass suggest that the nutrient allocation of seeds might be affected by both environment and plant traits. In addition, altitude and seed mass displayed partial overlapping effects on nutrient allocation of seeds. The negative effects of seed mass were affected slightly by altitude, whereas altitude only had a significant positive effect on P content when seed mass was controlled. Above all, seed P content showed obvious and general correlations with seed mass, altitude and age of clade, which indicated that higher seed P content might be an adaptive selection of species associated with growth and survival of progeny.
We hypothesize that the tumor necrosis factor-α (TNF-α) may play a role in disturbing the effect of selective serotonin reuptake inhibitor (SSRI) on the striatal connectivity in patients with major depressive disorder (MDD).
We performed a longitudinal observation by combining resting-state functional magnetic resonance imaging (rs-fMRI) and biochemical analyses to identify the abnormal striatal connectivity in MDD patients, and to evaluate the effect of TNF-α level on these abnormal connectivities during SSRI treatment. Eighty-five rs-fMRI scans were collected from 25 MDD patients and 35 healthy controls, and the scans were repeated for all the patients before and after a 6-week SSRI treatment. Whole-brain voxel-wise functional connectivity (FC) was calculated by correlating the rs-fMRI time courses between each voxel and the striatal seeds (i.e. spherical regions placed at the striatums). The level of TNF-α in serum was evaluated by Milliplex assay. Factorial analysis was performed to assess the interaction effects of ‘TNF-α × treatment’ in the regions with between-group FC difference.
Compared with controls, MDD patients showed significantly higher striatal FC in the medial prefrontal cortex (MPFC) and bilateral middle/superior temporal cortices before SSRI treatment (p < 0.001, uncorrected). Moreover, a significant interaction effect of ‘TNF-α × treatment’ was found in MPFC-striatum FC in MDD patients (p = 0.002), and the significance remained after adjusted for age, gender, head motion, and episode of disease.
These findings provide evidence that treatment-related brain connectivity change is dependent on the TNF-α level in MDD patients, and the MPFC-striatum connectivities possibly serve as an important target in the brain.
We previously reported four heterozygous missense mutations of MYH7, KCNQ1, MYLK2, and TMEM70 in a single three-generation Chinese family with dual Long QT and hypertrophic cardiomyopathy phenotypes for the first time. However, the clinical course among the family members was various, and the potential myocardial dysfunction has not been investigated.
The objective of this study was to investigate the echocardiographic and electrocardiographic characteristics in a genetic positive Chinese family with hypertrophic cardiomyopathy and further to explore the association between myocardial dysfunction and electric activity, and the identified mutations.
A comprehensive echocardiogram – standard two-dimensional Doppler echocardiography and three-dimensional speckle tracking echocardiography – and electrocardiogram were obtained for members in this family.
As previously reported, four missense mutations – MYH7-H1717Q, KCNQ1-R190W, MYLK2-K324E, and TMEM70-I147T – were identified in this family. The MYH7-H1717Q mutation carriers had significantly increased left ventricular mass indices, elevated E/e’ ratio, deteriorated global longitudinal stain, but enhanced global circumferential and radial strain compared with those in non-mutation patients (all p<0.05). The KCNQ1-R190W carriers showed significantly prolonged QTc intervals, and the MYLK2-K324E mutation carriers showed inverted T-waves (both p<0.05). However, the TMEM70-I147T mutation carriers had similar echocardiography and electrocardiographic data as non-mutation patients.
Three of the identified four mutations had potential pathogenic effects in this family: MYH7-H1717Q was associated with increased left ventricular thickness, elevated left ventricular filling pressure, and altered myocardial deformation; KCNQ1-R190W and MYLK2-K324E mutations were correlated with electrocardiographic abnormalities reflected in long QT phenotype and inverted T-waves, respectively.
This study aimed to investigate the applications of intelligent 256-slice computed tomography (iCT) perfusion imaging in high-voltage electrical injuries (HVEIs).
256-slice iCT was used to perform perfusion scanning for 48 patients with HVEI to detect the perfusion parameters.
The blood flow (BF) and peak enhancement intensity (PEI) values of the plane lower than the amputation level of the diseased side (ALD) were smaller than those of the corresponding healthy side (P<0.05); therefore, the differences were statistically significant. The BF value of the plane beyond the ALD was bigger than that of the ALD (t=2.99 and P=0.042); therefore, the difference was statistically significant. The BF, PEI, and blood volume values of the plane below the ALD were smaller than those of the ALD (P<0.05); therefore, the differences were statistically significant.
The technique of 256-slice iCT perfusion imaging could provide richer and more comprehensive imaging data for the clinical treatment of HVEIs, thus exhibiting its benefit in reducing the disability of patients with HVEIs. (Disaster Med Public Health Preparedness. 2018;12:478–485)
Children acquiring sociolinguistic knowledge in transnational migration settings must learn to evaluate multiple languages and dialects in a fluid, multifaceted social landscape. This study examines the sociolinguistic development of local and expatriate children in Singapore and investigates the extent to which they share sociolinguistic knowledge and norms. One hundred fourteen children ages five to nineteen completed a region identification task and an occupation judgment task, focusing on their perception of four regional English varieties: Australian English, Northern-China-accented English, Filipino English, and Singapore English. While all groups performed well on the region identification task, expatriate children outperformed locals within the youngest age group. Singaporean and expatriate children attending local schools showed greater familiarity with local norms than international school students in their occupation ratings. Participants mapped speakers to occupations by general prestige level, suggesting that children rely on indirect knowledge of social status rather than direct experience with speakers in their development of sociolinguistic evaluation. (Children's sociolinguistic development, transnational migration, language attitudes)*
Researches have suggested Mediterranean diet might lower the risk of chronic diseases, but data on skeletal muscle mass (SMM) are limited. This community-based cross-sectional study examined the association between the alternate Mediterranean diet score (aMDS) and SMM in 2230 females and 1059 males aged 40–75 years in Guangzhou, China. General information and habitual dietary information were assessed in face-to-face interviews conducted during 2008–2010 and 3 years later. The aMDS was calculated by summing the dichotomous points for the items of higher intakes of whole grain, vegetables, fruits, legumes, nuts, fish and ratio of MUFA:SFA, lower red meat and moderate ethanol consumption. The SMM of the whole body, limbs, arms and legs were measured using dual-energy X-ray absorptiometry during 2011–2013. After adjusting for potential covariates, higher aMDS was positively associated with skeletal muscle mass index (SMI, SMM/height2, kg/m2) at all of the studied sites in males (all Ptrend<0·05). The multiple covariate-adjusted SMI means were 2·70 % (whole body), 2·65 % (limbs), 2·50 % (arms) and 2·70 % (legs) higher in the high (v. low) category aMDS in males (all P<0·05). In females, the corresponding values were 1·35 % (Ptrend=0·03), 1·05, 0·52 and 1·20 %, (Ptrend>0·05). Age-stratified analyses showed that the favourable associations tended to be more pronounced in the younger subjects aged less than the medians of 59·2 and 62·2 years in females and males (Pinteraction>0·10). In conclusion, the aMDS shows protective associations with SMM in Chinese adults, particularly in male and younger subjects.
Brief cognitive–behavioural therapy (CBT) is an emerging treatment for
schizophrenia in community settings; however, further trials are needed,
especially in non-Western countries.
To test the effects of brief CBT for Chinese patients with schizophrenia
in the community (trial registration: ChiCTR-TRC-13003709).
A total of 220 patients with schizophrenia from four districts of Beijing
were randomly assigned to either brief CBT plus treatment as usual (TAU)
or TAU alone. Patients were assessed at baseline, post-treatment and at
6- and 12-month follow-ups by raters masked to group allocation.
At the post-treatment assessment and the 12-month follow-up, patients who
received brief CBT showed greater improvement in overall symptoms,
general psychopathology, insight and social functioning. In total, 37.3%
of those in the brief CBT plus TAU group experienced a clinically
significant response, compared with only 19.1% of those in the TAU alone
group (P = 0.003).
Brief CBT has a positive effect on Chinese patients with schizophrenia in
The goal to be achieved in this chapter is to analyze existing legal arrangements to cover civil liability for offshore incidents. In addition, a number of related regimes will be discussed equally dealing with catastrophic risk because they may constitute interesting examples for a liability regime for offshore-related risks. It is of course impossible to discuss all existing legal arrangements. We will therefore focus on the legal regime in some EU Member States, from which we have obviously selected Member States that have many offshore installations and thus a larger exposure to potential liability. However, a highly interesting non-EU country is Norway. As Chapter 2 indicated, Norway has an impressive number of offshore installations, and therefore, an analysis of its legal regime is important as well. In addition to the European Union, the civil liability regime of some other major offshore nations such as the United States and Australia will be briefly addressed. Moreover, it also may be interesting to look at regional, multi-lateral and bilateral arrangements, as well as at the way civil liability is dealt with in other high-risk sectors (e.g. in particular, the nuclear industry). Looking at the nuclear industry may constitute an interesting example of how a liability regime for offshore installations could be shaped as well, or at least the study of the nuclear liability regime may show some problematic aspects from which a potential EU offshore liability regime could learn. Therefore, the nuclear liability regime will be analyzed in a rather detailed way. The reason is especially that the international nuclear liability regime has been the subject of a lot of criticism because of low limits on the liability of nuclear power plant operators and because of public funding of the compensation. In this respect, a comparison with the US Price-Anderson Act is quite interesting because public funding is absent, and moreover, a system of retrospective pooling is introduced which does not necessitate money to be paid ex ante but is based rather on ex post retrospective premiums. This may be an interesting model for the compensation for damage caused by offshore installations as well.
The remainder of this chapter is structured as follows: first, the international legal framework will be presented (3.2); then some regional arrangements concerning offshore liability regimes will be discussed (3.3).
Epidemiological data show that osteoarthritis (OA) is significantly associated with lower birth weight, and that OA may be a type of fetal-originated adult disease. The present study aimed to investigate the prenatal food-restriction (PFR) effect on the quality of articular cartilage in female offspring to explore the underlying mechanisms of fetal-originated OA. Maternal rats were fed a restricted diet from gestational day (GD) 11 to 20 to induce intra-uterine growth retardation. Female fetuses and female adult offspring fed a post-weaning high-fat diet were killed at GD20 and postnatal week 24, respectively. Serum and knee cartilage samples from fetuses and adult female offspring were collected and examined for cholesterol metabolism and histology. Fetal serum corticosterone and insulin-like growth factor-1 (IGF-1) in the PFR group were lower than those of the control, but the serum cholesterol level was not changed. The lower expression of IGF-1 in the PFR group lasted into adulthood. The expression of extracellular matrix (ECM) genes, including type II collagen, aggrecan and cholesterol efflux genes including liver X receptor, were significantly induced, but the ATP-binding-cassette transporter A1 was unchanged. PFR could induce a reduction in ECM synthesis and impaired cholesterol efflux in female offspring, and eventually led to poor quality of articular cartilage and OA.
Cancer patients with depression or anxiety have poor survival, and the interaction between mental and physical problems in older patients may exacerbate this problem. K-ras oncogene (KRAS) mutation may play a role in the development of psychosocial distress and may be associated with poor survival of metastatic colorectal cancer (mCRC) patients. This study investigated the association between KRAS gene mutations and psychosocial morbidity to explore the possible cancer/psychosis relationship in older mCRC patients.
In this study, 62 newly diagnosed mCRC patients were recruited and completed the Hospital Anxiety and Depression Scale (HADS). Demographic data were also collected, and clinicopathological data were retrieved from medical records. KRAS mutations were assessed via PCR analysis of tissue specimens from the patients.
The results showed that 28 of the 62 participants (45.2%) had positive screens for possible depression, and 45 of the 62 participants (72.6%) had positive screens for anxiety. The KRAS mutation rate was 40.3% (25/62), and 19 of the 25 patients with KRAS mutations (76.0%) had probable depression, whereas only 24.3% of the patients with wild-type KRAS were probably depressed (p < 0.05). The KRAS mutation was associated with higher HADS depression scores, independent of gender and performance status (p < 0.05), but not with higher HADS anxiety or total scores.
KRAS mutations were associated with depression severity and higher rates of probable depression in older mCRC patients. Depression should be assessed and treated as early as possible in older mCRC patients with the KRAS mutation. Further studies are needed to verify our current findings using a larger sample size.
This study examined the development of and possible predictors of interrogative forms and functions in early childhood Mandarin. All the interrogatives drawn from the Early Child Mandarin Corpus (168 children 2;6, 3;6, 4;6, and 5;6) were analyzed. The main results indicated that (i) there were significant age effects in interrogative forms and functions, with the periods between the ages of 3;6 and 4;6 and between the ages of 2;6 and 3;6 being critical in the early acquisition of interrogative forms and functions, respectively; (ii) the form–function preference was verified, with wh-questions being primarily used to seek information (RfI), and intonation/echo and rhetorical questions being used to request action (RfA); (iii) more than half (59·5%) of the Mandarin interrogatives were used for RfI, whereas only 38·9% of them were used for RfA; and (iv) age, TV viewing time, and parent–child conversation time were the significant predictors of interrogative development.
Iron is an essential trace element that plays important roles in the cellular function of all organs and systems. However, the function of Fe(II) in mammalian embryo development is unknown. In this study, we investigated the role of Fe(II) during preimplantation embryo development. Depletion of Fe(II) using thiosemicarbazone-24 (TSC24), a specific Fe(II) chelator, rescued quenching of the Fe(II)-sensitive fluorophore phen green-SK. After in vitro fertilization, TSC24 significantly reduced the cleavage rate as well as blastocyst formation. The hatch rate of blastocysts was also reduced with 1 pM TSC24 treatment (20.25±1.86 versus 42.28±12.96%, p<0.05). Blastocysts were cultured in leukemia inhibitory factor-free mouse embryonic stem cell culture medium with or without TSC24, and those with depleted Fe(II) displayed delayed attachment and lost the ability to induce embryoid body formation. To further explore the mechanism of Fe(II) in embryo development, we assessed the expression of 5-hydroxymethylcytosine (5hmC) and OCT4 in the pronuclear and blastocyst stages, respectively. We observed that Fe(II) reduced 5hmC and OCT4 expression, which could be explained by low ten-eleven translocation (TET) enzyme activity induced by TSC24 treatment. These findings demonstrate that Fe(II) is required for mammalian embryo development and that it facilitates the process via regulation of TET activity.
X-ray powder diffraction data, unit-cell parameters, and space group for calcium(II)–naproxen complex, C28H26CaO6·2H2O, are reported [a = 36.918(2) Å, b = 5.655(6) Å, c = 12.505(6) Å, β = 91.263(2)°, cell volume V = 2610.47 Å3, Z = 4, and space group C2]. All measured lines were indexed and are consistent with the C2 space group. No detectable impurities were observed.