Search

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10 - 26 ). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10 -3 ). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Phosphorus is a key nutrient for all plant species and a limiting factor for grassland ecosystem function. In recent years, in response to the rapid increase of global nitrogen deposition, soil phosphorus contents and phosphatase activities changed to varying degrees in grassland ecosystems. We conducted a meta-analysis to examine the responses of soil pH, total phosphorus (TP), available phosphorus (AP), as well as activities of alkaline phosphatase (AlP) and acid phosphatase (AcP) in soils to nitrogen addition amount, nitrogen type, experimental duration, and sampling depth. The correlation between soil pH and phosphatase response ratio was investigated. The results showed that nitrogen addition significantly reduced soil pH, TP and AlP activity, while significantly increased AcP activity, but had no significant effect on AP. Soil pH and AlP activity significantly decreased under nitrogen addition >5 g·m -2 ·a -1 , and AcP activity significantly increased under high nitrogen addition (>10 g·m -2 ·a -1 ). The contents of TP and AP significantly decreased when nitrogen addition was 5-10 g·m -2 ·a -1 . NH 4 NO 3 treatment significantly reduced soil TP and increased AcP activity, while urea treatment significantly reduced soil pH and AlP activity. Across all nitrogen addition amounts, when the experiment duration was 3 to 10 years, soil TP content and AlP activity were significantly reduced. Soil pH was significantly reduced after three years nitrogen addition, and AcP activitiy was significantly increased after 10 years nitrogen addition. In the 0-10 cm soil layer, the TP content and AlP activity significantly decreased, while the AP content significantly increased. In >10 cm soil layer, the AP content was significantly decreased. The significant negative correlation between soil pH and AcP activity indicated that change in soil pH caused by nitrogen addition may be an important factor for the variation of soil phosphatase activity.

Urease in soil, as the most important enzyme catalyzing urea hydrolysis, plays an important role in nitrogen supply of grassland ecosystems. While the effects of different carbon additions on extracellular urease in grassland soil are well understood, their effects on soil intracellular urease remain unknow. Moreover, whether the responses of intracellular and extracellular urease to carbon additions are consistent need to be clarified. With a field experiment in Hulun Buir grassland of Inner Mongolia, we investigated soil intracellular and extracellular urease activities in chernozem under four treatments, including carbon-free (C 0 ), 250 (C 250 ), and 500 (C 500 ) kg C·hm -2 ·a -1 , using glucose as carbon source. Further, we analyzed their relationships with soil properties. Carbon additions significantly increased soil intracellular urease activity and its ratio to total urease activities and total urease activity, but did not affect soil extracellular urease activities. There was significant positive correlation between soil intracellular urease activity and microbial biomass, suggesting that the increases of soil intracellular urease activities were mainly caused by the increases of microbial biomass. Results of structural equation modeling (SEM) analysis showed that carbon additions indirectly increased soil intracellular urease activities by affecting microbial biomass.

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk., (Published 2014. This article is a US Government work and, as such, is in the public domain of the United States of America.)

Objective: To understand the dynamic of Oncomelania hupensis snail status in Duchang County at north shore of Poyang Lake, so as to provide the evidence for formulating the strategy of schistosomiasis control., Methods: The data about the snail status in Duchang County from 2005 to 2012 were collected, and the change trend of the snail status was analyzed. Results From 2005 to 2012, all the average density of living snails, the occurrence rate of frames with living snails, the density of infected snails and the area with infected snails showed a trend of sharp decline, and stayed at a low level. Compared to 2005, the above 4 indexes in 2008 decreased by 70.06%, 90.33%, 79.48%, and 37.88%, respectively, and those in 2012 decreased by 99.35%, 98.98%, 99.33%, and 93.84%, respectively. The infection rates of snails fluctuated between 0.06% and 0.53%, which showed a trend of first decrease and then increase. The snail area maintained at the level of 2052.5 hm2 since 2007., Conclusions: Most of the indexes of the snail status in Duchang County have decreased to the lowest level in history since 2012, but the snail area is stable and the infection rate of snails shows a fluctuation trend, which suggests that the risks of schistosomiasis transmission still exist, and the snail control still should be strengthened.

To identify risk factors for HIV infection among men who have sex with men (MSM) and to provide a theoretical basis for prevention interventions. Between December 2011 and August 2012, a case-control study was conducted among MSM who underwent voluntary counselling and testing for HIV. Confirmed HIV-positive MSM were included in the case group, and HIV-negative MSM were included in the control group. Information on possible risk factors was collected by a survey questionnaire and a qualitative interview. The results of a conditional logistic regression showed that the following were influencing factors for HIV infection: average monthly income between 2001 and 3000 Yuan (odds ratio (OR)=6.341, 95% CI: 1.714-12.544), only sometimes using condoms when having anal sex with men in the last 6 months (OR=7.601, 95% CI: 1.359-23.083), having HIV-positive sex partners (OR=5.273, 95% CI: 1.572-17.691), rectal trauma with bleeding in the last 6 months (OR=2.947, 95% CI: 1.308-6.638), not using condoms at last sexual encounter (OR=1.278, 95% CI: 1.012-5.595), engaging in commercial sex (OR=5.925, 95% CI: 1.923-13.890) and having more than 16 sex partners in the last 6 months (OR=1.175, 95% CI: 1.021-1.353). These seven factors were the risk factors of HIV infection (OR>1). However, having anal sex less than 10 times in the previous 1 month (OR=0.002, 95% CI: 0.000-0.287) was a protective factor against HIV infection among MSM (OR<1), and insertive (OR=0.116, 95% CI: 0.000-0.236) (OR<1) anal intercourse influenced HIV infection. Interventions should be targeted at MSM whose average monthly income is between 2001 and 3000 Yuan, and who engage in commercial sex. In addition, the importance of using condoms at every sexual encounter should be emphasised in health education, as should the treatment of rectal trauma with bleeding. Finally, MSM should decrease the number of sex partners and frequency of anal sex to decrease the rate of HIV infection.

Bifidobacterium and Lactobacillus can beneficially affect the host by producing acetic acid and lactic acid, which lower pH and thereby inhibit the growth of pathogens or allow the probiotic bacteria to compete with pathogens for epithelial adhesion sites and nutrients. The transmural migration of enteric organisms into the peritoneal cavity can cause peritonitis in peritoneal dialysis (PD) patients. We hypothesized that the composition of the intestinal microbiota with regard to Lactobacillus species and Bifidobacterium species differed between PD patients and healthy controls. The aim of the study was to investigate these differences by real-time PCR analysis of fecal samples. From 1 August 2009 to 31 March 2010, a total of 29 nondiabetic PD patients and 41 healthy controls from China Medical University Hospital were recruited after giving their informed consent. Fecal samples were collected from the PD patients and their age-matched counterparts in the morning using a standardized procedure. DNA extracted from these samples was analyzed by real-time PCR. All bifidobacteria, Bifidobacterium catenulatum, B. longum, B. bifidum, Lactobacillus plantarum, L. paracasei, and Klebsiella pneumoniae were less frequently detected in the patient samples. Dysbiosis (microbial imbalance) may impair intestinal barrier function and increase host vulnerability to pathogen invasion. Further studies are necessary to confirm our findings before clinical trials with probiotic supplementation in PD patients.

Background: Congenital central hypoventilation syndrome (CCHS) is characterized by compromised chemoreflexes resulting in sleep hypoventilation. We report a Chinese family with paired-like homeobox 2B (PHOX2B) mutation-confirmed CCHS, with a clinical spectrum from newborn to adulthood, to increase awareness of its various manifestations., Methods: After identifying central hypoventilation in an adult man (index case), clinical evaluation was performed on the complete family, which consisted of the parents, five siblings, and five offspring. Pulmonary function tests, overnight polysomnography, arterial blood gas measurements, hypercapnia ventilatory response, and PHOX2B gene mutation screening were performed on living family members. Brain MRI, 24-h Holter monitoring, and echocardiography were performed on members with clinically diagnosed central hypoventilation., Results: The index patient and four offspring manifested clinical features of central hypoventilation. The index patients had hypoxia and hypercapnia while awake, polycythemia, and hematocrit levels of 70%. The first and fourth children had frequent cyanotic spells, and both died of respiratory failure. The second and third children remained asymptomatic until adulthood, when they experienced impaired hypercapnic ventilatory response. The third child had nocturnal hypoventilation with nadir pulse oximetric saturation of 59%. Adult-onset CCHS with PHOX2B gene mutation of the + 5 alanine expansions were confirmed in the index patient and the second and third children. The index patient and the third child received ventilator support system bilevel positive airway pressure treatment, which improved the hypoxemia, hypercapnia, and polycythemia without altering their chemosensitivity., Conclusions: Transmission of late-onset CCHS is autosomal-dominant. Genetic screening of family members of CCHS probands allows for early diagnosis and treatment.

Objective: There has been increasing evidence that angiotensin II may play an important role in the pathogenesis and in the evolution of acute lung injury. It was therefore hypothesized that polymorphisms of the angiotensin-converting enzyme gene affects the risk and outcome of acute respiratory distress syndrome (ARDS)., Design: Prospective, observational study., Patients and Settings: The ARDS group consisted of 101 patients treated at the medical intensive care unit; the control groups consisted of 138 "at-risk" patients treated at the medical intensive care unit due to acute respiratory failure but did not meet the ARDS criteria throughout the hospital course, and 210 non-at-risk subjects., Intervention: None., Measurements and Main Results: The ARDS patients and control subjects were genotyped for the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene. Association of the polymorphism and the risk and the outcome of ARDS was analyzed. There was no significant difference in the frequencies of the genotypes between the ARDS, at-risk, and non-at-risk groups. The 28-day mortality rates were significantly different between the three angiotensin-converting enzyme genotypes (42%, 65%, and 75% for II, ID, and DD, respectively; p = .036). Survival analysis showed that the II genotype favorably affected 28-day survival (hazard ratio, 0.46; 95% confidence interval, 0.26-0.81; p = .007), whereas ARDS caused by hospital-acquired pneumonia had a negative effect (hazard ratio, 2.34; 95% confidence interval, 1.25-4.40; p = .008). The II genotype (hazard ratio, 0.53; 95% confidence interval, 0.32-0.87; p = .012) and ARDS caused by hospital-acquired pneumonia (hazard ratio, 2.13; 95% confidence interval, 1.24-3.68; p = .006) were also significant prognostic factors for the in-hospital mortality., Conclusions: The angiotensin-converting enzyme I/D polymorphism is a significant prognostic factor for the outcome of ARDS. Patients with the II genotype have a significantly better chance of survival. This study did not show an increased risk for ARDS in Chinese patients with the D allele.

Lipoprotein lipase (LPL) plays a crucial role in the regulation of lipoprotein metabolism by hydrolyzing the core triglycerides of circulating chylomicrons and very low-density lipoprotein. Deficiency in this enzyme usually results in disturbances in lipid levels. To understand the molecular defect that leads to a functional deficiency of LPL in patients with hypertriglyceridemia, we looked for mutations of the LPL gene by means of single-strand conformation polymorphism (SSCP) analysis and direct DNA sequencing in 24 patients. A single base C-->G substitution in codon 252 of the LPL gene, encoding a change of a leucine to a valine residue in the mature protein, was found in three women who had hypertriglyceridemia and recurrent pancreatitis. Two of these patients, who were homozygous for the L252V mutation, had variable and occasionally severe hypertriglyceridemia with undetectable or very low LPL activities, respectively. The third woman was heterozygous for this mutation. All three patients had poor post-heparin LPL activity. Site-directed mutagenesis experiments provided in vitro evidence that the mutation of codon 252 was responsible for the loss of LPL activity. In conclusion, we identified a novel LPL mutation that results in decreased LPL activity in Taiwanese patients with hypertriglyceridemia. The assessment of a causative link between the mutation and hyperlipidemia awaits further studies.