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In order to obtain a 1053 nm output laser with a high beam quality, the mode distribution of the YLF solid laser with a plane-plane resonator is studied. According to the Collins theory, the influences of the position and size parameters of a Gaussian aperture on the mode of the output beam is simulated and analyzed. Compared with the simulation results without a Gaussian aperture, the Gaussian aperture in the cavity can significantly improve the quality of the output laser. Based on the theoretical simulations, a laser with optimal structural parameters is built. The profiles and mode distributions of the laser output beams with a Gaussian aperture and without a Gaussian aperture in the cavity are measured, respectively. When the radius of the light spot on the film of the Gaussian aperture is 4 mm and the distance between the Gaussian aperture and total-reflection mirror is 30 mm, a 1053 nm laser output with the values of M2 in the x and y directions of 1.9 and 1.8, and maximum output power of 9.7 W is obtained. The experimental results demonstrate that the Gaussian aperture in the cavity can improve the mode distribution of the cavity and obtain the laser output with a higher beam quality, which is basically consistent with the results of theoretical simulations.

In this paper, a continuous wave (CW) and rhenium disulphide (ReS2) passively Q-switched Nd:GdTaO4 laser under the pump at 879 nm was firstly reported. CW output characteristics under indirect 808 nm pumping and direct 879 nm pumping were investigated, respectively. By comparison with indirect pumping, the direct pump at 879 nm effectively relieved thermal lenses effect. Under direct pumping, the maximum CW output power was 5.1 W with slope efficiencies (ηs) of 48.6%. In the indirect pumping a maximum CW output power of 4.3 W was obtained, corresponding to ηs of 41.2%. A ReS2 nanosheet was utilized to achieve the pulsed laser output. At absorbed pump power of 7.1 W, the highest repetition rate, narrowest pulse width, maximum average output power, single pulse energy, and peak power reached 67 kHz, 230 ns, 1 W, 14.93 μJ, and 64.9 W, respectively.

// Chen Hu 1, 2, * , Aoli Wang 1, 2, * , Hong Wu 1, 3, * , Ziping Qi 1, 3, * , Xixiang Li 1, 3, * , Xiao-E Yan 4, * , Cheng Chen 1, 2 , Kailin Yu 1, 2 , Fengming Zou 1, 3 , Wenchao Wang 1, 3 , Wei Wang 1, 3 , Jiaxin Wu 1, 2 , Juan Liu 1, 2 , Beilei Wang 1, 2 , Li Wang 1, 2 , Tao Ren 5 , Shanchun Zhang 3, 6 , Cai-Hong Yun 4 , Jing Liu 1, 3 , Qingsong Liu 1, 2, 3, 5 1 High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031, P. R. China 2 University of Science and Technology of China, Hefei, Anhui 230036, P. R. China 3 CHMFL-HCMTC Target Therapy Joint Laboratory, Hefei, Anhui 230031, P. R. China 4 Institute of Systems Biomedicine, Department of Biophysics, Beijing Key Laboratory of Tumor Systems Biology and Center for Molecular and Translational Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P.R. China 5 Precision Targeted Therapy Discovery Center, Institute of Technology Innovation, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230088, P. R. China 6 Hefei Cosource Medicine Technology Co. LTD., Hefei, Anhui 230031, P. R. China * These authors have contributed equally to this work Correspondence to: Cai-Hong Yun, email: yunch@hsc.pku.edu.cn Jing Liu, email: jingliu@hmfl.ac.cn Qingsong Liu, email: qsliu97@hmfl.ac.cn Keywords: EGFR, EGFRT790M, NSCLC, kinase inhibitors, drug resistance Received: December 09, 2016 Accepted: January 23, 2017 Published: February 17, 2017 ABSTRACT EGFR T790M mutation accounts for about 40-55% drug resistance for the first generation EGFR kinase inhibitors in the NSCLC. Starting from ibrutinib, a highly potent irreversible BTK kinase inhibitor, which was also found to be moderately active to EGFR T790M mutant, we discovered a highly potent irreversible EGFR inhibitor CHMFL-EGFR-26, which is selectively potent against EGFR mutants including L858R, del19, and L858R/T790M. It displayed proper selectivity window between the EGFR mutants and the wide-type. CHMFL-EGFR-26 exhibited good selectivity profile among 468 kinases/mutants tested (S score (1)=0.02). In addition, X-ray crystallography revealed a distinct “DFG-in” and “cHelix-out” inactive binding mode between CHMFL-EGFR-26 and EGFR T790M protein. The compound showed highly potent anti-proliferative efficacy against EGFR mutant but not wide-type NSCLC cell lines through effective inhibition of the EGFR mediated signaling pathway, induction of apoptosis and arresting of cell cycle progression. CHMFL-EGFR-26 bore acceptable pharmacokinetic properties and demonstrated dose-dependent tumor growth suppression in the H1975 (EGFR L858R/T790M) and PC-9 (EGFR del19) inoculated xenograft mouse models. Currently CHMFL-EGFR-26 is undergoing extensive pre-clinical evaluation for the clinical trial purpose.

In this paper, a continuous wave (CW) and two-dimensional (2D) tin diselenide (SnSe2) and palladium diselenide (PdSe2) passively Q-switched Nd:GdNbO4 laser under direct pumping was demonstrated for the first time. The CW laser performance under the pump at 879 nm was compared to that using traditional 808 nm pumping. The 2D SnSe2 and PdSe2 nanosheets were synthesized by chemical vapor deposition (CVD) technique. The optical properties and microstructures of two nanosheets were investigated. In the passively Q-switched operation, the highest repetition rate, narrowest pulse width, maximum pulse energy and peak power of SnSe2/Nd:GdNbO4 laser were 160 kHz, 555 ns, 2.3 μJ and 4.2 W, respectively. And for PdSe2/Nd:GdNbO4 laser, the corresponding values were 143 kHz, 530 ns, 3.7 μJ and 7.0 W, respectively.

// Xiaochuan Liu 1, 2, * , Aoli Wang 2, 3, * , Xiaofei Liang 2, 4, * , Juanjuan Liu 2, 3, * , Fengming Zou 2, 4, * , Cheng Chen 2, 4, * , Zheng Zhao 2, 4 , Yuanxin Deng 2, 3 , Hong Wu 2, 3 , Ziping Qi 2, 4 , Beilei Wang 2, 4 , Li Wang 2, 4 , Feiyang Liu 2, 3 , Yunhe Xu 1 , Wenchao Wang 2, 4 , Stacey M. Fernandes 5 , Richard M. Stone 5 , Ilene A. Galinsky 5 , Jennifer R. Brown 5 , Teckpeng Loh 1 , James. D. Griffin 5 , Shanchun Zhang 4, 6 , Ellen L. Weisberg 5 , Xin Zhang 2 , Jing Liu 2, 4 , Qingsong Liu 2, 3, 7 1 Department of Chemistry, University of Science and Technology of China, Anhui, Hefei, 230036, P. R. China 2 High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, Anhui, P. R. China 3 University of Science and Technology of China, Anhui, Hefei, 230036, P. R. China 4 CHMFL-HCMTC Target Therapy Joint Laboratory, Hefei, 230031, Anhui, P. R. China 5 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA 6 Hefei Cosource Medicine Technology Co. LTD. Hefei, 230031, Anhui, P.R.China 7 Hefei Science Center, Chinese Academy of Sciences, Hefei, 230031, Anhui, P. R. China * These authors have contributed equally to this work Correspondence to: Ellen L. Weisberg, email: Ellen_weisberg@dfci.harvard.edu Xin Zhang, email: xinzhang@hmfl.ac.cn Jing Liu, email: jingliu@hmfl.ac.cn Qingsong Liu, email: qsliu97@hmfl.ac.cn Keywords: PI3Kδ, Vps34, combination, chronic lymphatic leukemia, acute myeloid leukemia Received: April 19, 2016 Accepted: June 03, 2016 Published: July 18, 2016 ABSTRACT PI3Kδ has been found to be over-expressed in B-Cell-related malignancies. Despite the clinical success of the first selective PI3Kδ inhibitor, CAL-101, inhibition of PI3Kδ itself did not show too much cytotoxic efficacy against cancer cells. One possible reason is that PI3Kδ inhibition induced autophagy that protects the cells from death. Since class III PI3K isoform PIK3C3/Vps34 participates in autophagy initiation and progression, we predicted that a PI3Kδ and Vps34 dual inhibitor might improve the anti-proliferative activity observed for PI3Kδ-targeted inhibitors. We discovered a highly potent ATP-competitive PI3Kδ/Vps34 dual inhibitor, PI3KD/V-IN-01, which displayed 10-1500 fold selectivity over other PI3K isoforms and did not inhibit any other kinases in the kinome. In cells, PI3KD/V-IN-01 showed 30-300 fold selectivity between PI3Kδ and other class I PI3K isoforms. PI3KD/V-IN-01 exhibited better anti-proliferative activity against AML, CLL and Burkitt lymphoma cell lines than known selective PI3Kδ and Vps34 inhibitors. Interestingly, we observed FLT3-ITD AML cells are more sensitive to PI3KD/V-IN-01 than the FLT3 wt expressing cells. In AML cell inoculated xenograft mouse model, PI3KD/V-IN-01 exhibited dose-dependent anti-tumor growth efficacies. These results suggest that dual inhibition of PI3Kδ and Vps34 might be a useful approach to improve the PI3Kδ inhibitor’s anti-tumor efficacy.

// Su Hang 1, 2 , Agnes F.Y. Tiwari 1 , Hextan Y.S. Ngan 3 , Yim-Ling Yip 4 , Annie L.M. Cheung 4 , Sai Wah Tsao 4 , Wen Deng 1 1 School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China 2 College of Forensic Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shanxi Province, P.R. China 3 Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong, SAR, China 4 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China Correspondence to: Wen Deng, email: wdeng@hku.hk Keywords: cervical epithelial cells, immortalization, p16 INK4a , telomerase, HPV-negative Received: March 13, 2016 Accepted: May 29, 2016 Published: June 17, 2016 ABSTRACT Cervical epithelial cell immortalization with defined genetic factors without viral oncogenes has never been reported. Here we report that HPV-negative cervical epithelial cells failed to be immortalized by telomerase activation or the combination of p53 knockdown and telomerase activation. Under those conditions, p16 INK4a expression was always elevated during the late stage of limited cell lifespan, suggesting that cervical epithelial cells possess an intrinsic property of uniquely stringent activation of p16 INK4a , which may offer an explanation for the rarity of HPV-negative cervical cancer. Combining p16 INK4a knockdown with telomerase activation resulted in efficient immortalization of HPV-negative cervical epithelial cells under ordinary culture conditions. Compared with the HPV16-E6E7-immortalized cell lines derived from the same primary cell sources, the novel HPV-negative immortalized cell lines had lower degrees of chromosomal instability, maintained more sensitive p53/p21 response to DNA damage, exhibited more stringent G2 checkpoint function, and were more resistant to replication-stress-induced genomic instability. The newly immortalized HPV-negative cervical epithelial cell lines were non-tumorigenic in nude mice. The cell lines can be used not only as much-needed HPV-negative non-malignant cell models but also as starting models that can be genetically manipulated in a stepwise fashion to investigate the roles of defined genetic alterations in the development of HPV-negative cervical cancer.

// Xiaochuan Liu 1, 2, * , Aoli Wang 2, 3, * , Xiaofei Liang 2, 4, * , Cheng Chen 2, 4, * , Juanjuan Liu 2, 3 , Zheng Zhao 2, 4 , Hong Wu 2, 3 , Yuanxin Deng 2, 3 , Li Wang 2, 4 , Beilei Wang 2, 4 , Jiaxin Wu 2, 3 , Feiyang Liu 2, 3 , Stacey M. Fernandes 5 , Sophia Adamia 5 , Richard M. Stone 5 , Ilene A. Galinsky 5 , Jennifer R. Brown 5 , James D. Griffin 5 , Shanchun Zhang 4, 6 , Teckpeng Loh 1 , Xin Zhang 2 , Wenchao Wang 2, 4 , Ellen L. Weisberg 5 , Jing Liu 2, 4 , Qingsong Liu 2, 4, 7 1 Department of Chemistry, University of Science and Technology of China, Hefei 230036, Anhui, P. R. China 2 High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, Anhui, P. R. China 3 University of Science and Technology of China, Hefei 230036, Anhui, P. R. China 4 CHMFL-HCMTC Target Therapy Joint Laboratory, Hefei 230031, Anhui, P. R. China 5 Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA 6 Hefei Cosource Medicine Technology Co. LTD., Hefei 230031, Anhui, P. R. China 7 Hefei Science Center, Chinese Academy of Sciences, Hefei 230031, Anhui, P. R. China * These authors have contributed equally to this work Correspondence to: Wenchao Wang, email: wwcbo@hmfl.cas.cn Ellen L. Weisberg, email: Ellen_weisberg@dfci.harvard.edu Jing Liu, email: jingliu@hmfl.ac.cn Qingsong Liu, email: qsliu97@hmfl.ac.cn Keywords: PI3Kδ, leukemia, B-cell malignances, PI3K, kinase inhibitors Received: January 14, 2016 Accepted: March 28, 2016 Published: April 12, 2016 ABSTRACT PI3Kδ is predominately expressed in leukocytes and has been found overexpressed in B-cell related malignances such as CLL and AML. We have discovered a highly selective ATP competitive PI3Kd inhibitor PI3KD-IN-015, which exhibits a high selectivity among other PI3K isoforms in both biochemical assays and cellular assay, meanwhile did not inhibit most of other protein kinases in the kinome. PI3KD-IN-015 demonstrates moderately anti-proliferation efficacies against a variety of B-cell related cancer cell lines through down-regulate the PI3K signaling significantly. It induced both apoptosis and autophagy in B-cell malignant cell lines. In addition, combination of autophagy inhibitor Bafilomycin could potentiate the moderate anti-proliferation effect of PI3KD-IN-015. PI3KD-IN-015 shows anti-proliferation efficacy against CLL and AML patient primary cells. Collectively, these results indicate that PI3KD-IN-015 may be useful drug candidate for further development of anti-B-cell related malignances therapies.

The FLT3-ITD mutation is one of the most prevalent oncogenic mutations in AML. Several FLT3 kinase inhibitors have shown impressive activity in clinical evaluation, however clinical responses are usually transient and clinical effects are rapidly lost due to drug resistance. One of the resistance mechanisms in the AML refractory patients involves FLT3-ligand induced reactivation of AKT and/or ERK signaling via FLT3 wt kinase. Via a screen of numerous AKT kinase inhibitors, we identified the well-established orally available AKT inhibitor, A674563, as a dual suppressor of AKT and FLT3-ITD. A674563 suppressed FLT3-ITD positive AML both in vitro and in vivo. More importantly, compared to other FLT3 inhibitors, A674563 is able to overcome FLT3 ligand-induced drug resistance through simultaneous inhibition of FLT3-ITD- and AKT-mediated signaling. Our findings suggest that A674563 might be a potential drug candidate for overcoming FLT3 ligand-mediated drug resistance in FLT3-ITD positive AML.

A continuous wave (CW) and passively Q-switched 1 . 06 μ m Nd:GdLaNbO4 laser under direct 879 nm pumping is firstly reported in this paper. The CW output power and slope efficiency varied from 4.50 W and 45.6% to 6.55 W and 50.0% when the indirect pumping of 808 nm was changed to the direct pumping of 879 nm. Furthermore, the beam quality was also improved significantly. For the CW Nd:GdLaNbO4 laser, as is known to all that the highest output power with excellent beam quality was obtained. In the Q-switched operation, rhenium disulfide (ReS2) synthetized by chemical vapor deposition (CVD) method was employed as a saturable absorber (SA). The optical properties and atom force microscope (AFM) image of ReS2 were measured and recorded to characterize it. A maximum average output power with 312 mW, a narrowest pulse width with 400 ns, and a highest repetition rate with 147 kHz were obtained under the direct 879 nm pumping.

A comparison of the pulsed laser performances of 2 μm passively Q-switched Tm:YAlO3 (YAP) lasers based on the use of tungsten disulfide (WS2) and molybdenum disulfide (MoS2) two-dimensional (2D) nanosheets as saturable absorbers is reported. The novel nanosheets were prepared by chemical vapor deposition (CVD) technology. The microstructure and optical characteristics of the nanosheets were investigated experimentally. In a continuous-wave (CW) operation, the maximum output power of 2.8 W was obtained at an absorbed pump power of 6.9 W, with a corresponding slope efficiency of 46.4%. In a passively Q-switched operation at a pump power of 1.45 W, the average output power, pulse width, repetition rate, pulse energy, and peak power for the Tm:YAP/WS2 laser were 0.11 W, 2.65 μs, 34.7 kHz, 2.9 μJ, and 1.23 W, respectively. As for the Tm:YAP/MoS2 laser, the corresponding values were 0.10 W, 2.5 μs, 24.0 kHz, 3.8 μJ, and 1.55 W.

In this work, a novel two-dimensional palladium diselenide (PdSe2) nanosheet was synthesized by chemical vapour deposition method and used as a saturable absorber (SA) for generation of Q-switched laser pulses. The microstructure and optical properties of PdSe2 nanosheet were investigated. For laser emission, a newly developed Nd:GdLaNbO4 mixed crystal was used as the gain medium, while the pump was done with fiber-coupled diode laser at 879 nm, directly into the 4F3/2 emitting level. The Q-switched Nd:GdLaNbO4/PdSe2 laser yielded 405 mW average output power for 8.8 W absorbed pump power at 879 nm. The laser runs at 164 kHz with 2.47 μJ energy per pulse; pulse duration was 340 ns, indicating a pulse peak power of 7.26 W. These first results prove that PdSe2 nanosheet can be used as SA in passively Q-switch laser devices.

Objective To investigate ethnic difference in the associations of BMI with comorbidity, mortality, and body composition between mainland Chinese and U.S. whites. Methods Ethnic-comparison study using data from China Health and Nutrition Survey, U.S. National Health and Nutrition Examination Survey, and data from Zhejiang University (China) and Columbia University (U.S.). Results Chinese people experienced greater odds of comorbidities than whites for a given BMI after standardizing for age and sex: 43% for diabetes, 30% for dyslipidemia, 28% for hypertension, 38% for metabolic syndrome, and 48% for hyperuricemia. Comparisons of BMI-mortality associations found that the U-shaped BMI-mortality curve shifted 1-2 kg m(-2) to the left in Chinese compared to whites. Compared to whites at BMIs of 25 and 30 kg m(-2), corresponding cutoffs in Chinese were 22.5 and 25.9 kg m(-2) in men, and 22.8 and 26.6 kg m(-2) in women after both fat and fat distribution were taken into account. Conclusions Comorbidity, mortality, and body composition data consistently support the use of lower BMI cutoffs in Chinese than those in whites.

Objectives As the primary cause of lung cancer, whether smoking confers the same risk of lung cancer for women as men is unclear. Therefore, we aimed to compare male and female susceptibility for cigarette smoking-attributable lung cancer. Methods A systematic review and meta-analysis was conducted by searching articles published up to July 2013 in three online databases (MEDLINE, EMBASE, and Cochrane Database). All studies estimated the association of cigarette smoking with the risk of lung cancer between men and women, respectively. A random effects model with inverse variance weighting was used to pool data. Male to female ratio of relative risk (RRR) was calculated to compare male and female susceptibility for cigarette smoking-attributable lung cancer. Results 47 articles containing 404,874 individuals were included in the final analysis. Compared with non-smokers, male to female RRR was 1.61 (95%CI: 1.37, 1.89) among current smokers. Based on pathological type, adenocarcinoma had the highest RRR (1.42; 95%CI: 0.86, 2.35), followed by squamous cancer and small cell lung cancer. Furthermore, compared with non-smoking men, current smoking men had higher risk of lung cancer than women in spite of smoking quantity, smoking duration or years since quitting. Conclusions These findings indicated that males had higher susceptibility for cigarette smoking-attributable lung cancer than females. It is contradicted with traditional opinion that females would be more easily suffered from cigarette smoking-attributable health problems than males. Hence, tobacco control is very crucial in both males and females.

BACKGROUND Hypertensive disorders of pregnant women are one of the important causes of maternal and perinatal morbidity and mortality. Evidence showed mental stress might be a risk factor of gestational hypertensive disorders. OBJECTIVE The objective of this study was to evaluate the relationships between mental stress and gestational hypertension/preeclampsia in pregnant women. METHODS Relevant studies were identified by PubMed, Cochrane, Chinese medical datasets (Wanfang, CNKI, and VIP Database). Only case-control or cohort studies evaluating an association of preeclampsia or gestational hypertension with mental stress were included in the present meta-analysis. Essential information was extracted from the qualified studies. Odds ratio (OR) was used as a pooled effect size. Potential heterogeneity and publication bias were detected as well. RESULTS Thirteen studies were included in the final analyses, which totally recruited 668,005 pregnant women. The results indicated that mental stress was associated with an increased risk of gestational hypertension (OR, 1.26; 95% confidence interval [CI], 1.00-1.59; P = 0.047) and preeclampsia (OR, 1.49; 95%CI, 1.27-1.74; P < 0.001). Meanwhile, work stress (OR, 1.50; 95% CI, 1.15-1.97; P = 0.003) and anxiety or depression (OR, 1.88; 95%CI, 1.08-3.25; P = 0.02)were positively associated with risk of preeclampsia. CONCLUSIONS Mental stress during life or pregnancy may be a risk factor for gestational hypertension and preeclampsia among pregnant women.

The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)(AA+AG): 0.654, 95% confidence interval (CI): 0.406-1.055; P=0.082), rs4233532 (OR(CC): 1.667, 95% CI: 0.967-2.876; OR(CT): 1.435, 95% CI: 0.998-2.063; P=0.077), and rs2881930 (OR(CC): 0.263, 95% CI: 0.095-0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (OR(AA+AG): 1.233, 95% CI: 0.903-1.683), rs4233532 (OR(CC): 0.892, 95% CI: 0.640-1.243; OR(CT): 1.134, 95% CI: 0.897-1.433), and rs2881930 (OR(CC): 1.096, 95% CI: 0.620-1.938; OR(CT): 1.009, 95% CI: 0.801-1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319-2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.

OBJECTIVE To evaluate associations between adiposity trajectories over time and insulin sensitivity and glucose deterioration in a Chinese twin cohort. RESEARCH DESIGN AND METHODS This study focused on 341 males and 292 females aged 20–50 years at baseline who had physical clinical examinations and oral glucose tolerance test at two time points with an average of 6 years apart. BMI, waist circumference, percent body fat (PBF), and percent trunk fat (PTF) trajectories were classified into five track groups based on age- and sex-specific tertiles at each visit. We calculated the odds of the insulin sensitivity index(0,120) [ISI(0,120)] or glycemic deterioration at follow-up among five defined trajectories (tertilebaseline → tertilefollow-up) using generalized estimate equation models. Additionally, we applied structural equation models to examine genetic and environmental influences on adiposity, adiposity change over time (ACO), ISI(0,120), and the interrelationships among them. RESULTS Participants with stable adiposity (BMI, waist circumference, PBF, and PTF) in the highest tertile or shifting to the highest tertile tended to have the lowest ISI(0,120) at follow-up or experience glycemic deterioration. Genetic factors exerted the major influence on adiposity, but environmental factors unique to each twin contributed more strongly to ISI and ACO. Correlations between adiposity/ACO and insulin sensitivity were mainly due to environmental influences. CONCLUSIONS When adiposity stays or becomes high, insulin sensitivity falls and risk of glycemic deterioration rises. Additionally, we found that genetic factors exerted the major influence on adiposity, while environmental factors played the principal role for ACO and insulin sensitivity.

Objective To investigate the association between sleep duration and insulin resistance in rural Chinese adults and examine whether any such associations are independent of adiposity. Methods This is a cross-sectional analysis of 854 men and 640 women aged 20 to 70 years from the Anqing Twin Cohort. The following measures were obtained for each subject: Body mass index (BMI) and percentage of trunk fat (%TF), fasting plasma glucose, homeostatic model assessment of insulin resistance index (HOMA-IR), self-reported sleep duration and measures of snoring and sleep disturbance from the Pittsburgh Sleep Quality Indices (PSQI) questionnaire were modified for a Chinese population. Multivariate linear regressions were applied to examine the association of sleep duration with HOMA-IR, with and without adjustment for adiposity variables, along with other relevant covariates. Results In this sample of relatively lean rural Chinese adults, short sleep duration was associated with HOMA-IR in women but not in men. In women, short (⩽7 h/night) sleep duration was associated with a higher HOMA-IR ( p = 0.003) compared with normal sleep duration (>7 to ⩽8 h/night) after adjustment for all the covariates except adiposity. Further adjustment for BMI or %TF attenuated the sleep-HOMA-IR association, but the association remained significant upon adjustment for BMI ( p = 0.013); and upon adjustment for %TF ( p = 0.026). Long sleep duration (>8 h/night) was not significantly associated with HOMA-IR. Conclusion In this rural Chinese cohort, short sleep duration is independently associated with increased insulin resistance among women only, even after adjusting for adiposity and other potential confounders.

To cite this article: Liu X, Wang G, Hong X, Wang D, Tsai H-J, Zhang S, Arguelles L, Kumar R, Wang H, Liu R, Zhou Y, Pearson C, Ortiz K, Schleimer R, Holt P, Pongracic J, Price HE, Langman C, Wang X. Gene–vitamin D interactions on food sensitization: a prospective birth cohort study. Allergy 2011; 66: 1442–1448. Abstract Background: It has been hypothesized that vitamin D deficiency (VDD) contributes to the development of food sensitization (FS) and then food allergy. However, the epidemiological evidence is conflicting. We aim to examine whether cord blood VDD is associated with FS and whether such association can be modified by genetic variants in a prospective birth cohort. Methods: This study included 649 children who were enrolled at birth and followed from birth onward at the Boston Medical Center. We defined VDD as cord blood 25(OH)D

Context: Adipokines have been linked to bone phenotypes recently, but with conflicting results. Few such studies have been conducted in adolescents.Objective: The aim of the study was to examine the associations of adiponectin and leptin with multiple bone phenotypes in Chinese adolescents and estimate the genetic contribution to these associations.Design and Setting: This was a cross-sectional study conducted in rural China.Participants: A total of 675 males and 575 females aged 13–21 yr were included.Outcome Measures: Fat mass (FM), lean mass (LM), bone area (BA), bone mineral content (BMC), cross-sectional area (CSA), and section modulus (SM) were measured by dual-energy x-ray absorptiometry. Plasma adipokine concentration was determined using sandwich immunoassays.Results: Adiponectin was inversely associated with all BMCs in males (P < 0.01), but not in females, after adjusting for LM, body weight, or BMI singly, or for LM and FM simultaneously. No such relationships were observed for CSA or SM in both genders. Leptin was inversely associated with all BAs, total-hip BMC, CSA, and SM in both genders, when adjusting for body weight or BMI. These associations, except for whole-body BA and lumbar spine BA in females, disappeared when simultaneously adjusting for LM and FM. By Cholesky decomposition models using twin design, significant genetic correlations were detected between adiponectin and total-hip BMC in males and between leptin and total-hip BMC in both genders.Conclusions: We demonstrated that adiponectin and leptin were inversely associated with adolescent bone phenotypes but showed differential associations by gender, type of bone phenotypes, and adjustment of FM. This study also suggested that adipokines and bone phenotypes may share a common set of genes.

Background: Adolescence is a critical period for rising adiposity and falling insulin sensitivity (IS), but the independent relation between adiposity and IS remains understudied. Objective: The objective was to examine which adiposity measures are most strongly associated with IS in nondiabetic adolescents, whether sex-difference exists, and to what degree genetic or environmental factors affect the adiposity-IS relation. Design: The study included 1613 rural Chinese adolescents (888 males) aged 13–20 y from a population-based twin cohort. We used graphic plots and linear mixed models to examine the relation of anthropometric and dual-energy X-ray absorptiometry–based measures of adiposity with IS [QUantitative Insulin-sensitivity ChecK Index (QUICKI), fasting serum insulin (FSI), homeostasis model assessment of insulin resistance (HOMA-IR)] and structural equation models to estimate genetic/environmental influences on these associations. Results: In graphic analyses, participants in the highest quintile (quintile 5) of waist circumference (WC) and percentage body fat (%BF) had the lowest QUICKI and the highest FSI and HOMA-IR values for all age-sex groups. In regression models adjusted for age, Tanner stage, zygosity, and physical activity, all adiposity measures showed inverse associations with IS in both sexes, but WC explained the largest fraction of variance in IS measures (10–14%). Of the phenotypic correlations between adiposity measures and IS (−0.28 to −0.38), 74–85% were attributed to shared genetic factors and 15–26% to common unique environmental factors in both sexes. Conclusions: In these relatively lean Chinese adolescents, WC and %BF (quintile 5) are the adiposity measures most consistently and strongly associated with decreased IS in both sexes. To a large degree, shared genetic factors contribute to this association.

Context: Factors associated with the high prevalence of vitamin D deficiency in China are not well described, especially among Chinese adolescents. Objectives: The aim of the study was to examine important environmental or sociodemographic factors influencing 25-hydroxyvitamin D [25(OH)D] levels and estimate its heritability. Design: A sample of 226 male and female adolescent twins aged 13–20 yr from a large prospective twin cohort of rural Chinese children and adolescents that has been followed for 6 yr were evaluated. Main Outcome Measure(s): Blood level of 25(OH)D was measured using tandem mass spectrometry methodology. Results: The overall mean (sd) 25(OH)D level was 18.0 (9.4) ng/ml, with wide variation by gender and season. In males (47.4% of subjects), the mean (sd) 25(OH)D level was 12.1 (4.2) ng/ml in non-summer and 27.4 (8.8) ng/ml in summer; in females, it was 10.1 (4.1) ng/ml in non-summer and 19.5 (6.3) ng/ml in summer. A multivariate model that included gender, age, season, physical activity, and student status demonstrated that male gender, summer season, and high physical activity significantly increased 25(OH)D levels. Summer season and male gender also significantly decreased the risk of being in the lowest 25(OH)D tertile. Overall, 68.9% of the variability in 25(OH)D level was attributable to additive genetic influence. Stratification by gender found that in males, 85.9% of the variability in 25(OH)D level was attributable to such influence, but in females, it was only 17%. Conclusion: In this sample of rural Chinese adolescents, 25(OH)D level was influenced by gender, season, and physical activity level. There was a strong genetic influence on 25(OH)D level in males only.

Objective We compared the efficacy of folic acid (FA) plus enalapril with enalapril alone on the reduction of blood pressure (BP) and fasting plasma glucose (FPG) in adult Chinese hypertensive patients. Methods Four hundred eighty subjects with mild to moderate BP were randomly assigned to one of three treatment groups: 1) 10 mg of enalapril (control group), 2) 10 mg of enalapril plus 0.4 mg of FA (low-FA group), or 3) 10 mg of enalapril plus 0.8 mg of FA (high-FA group) daily for 8 wk. Generalized linear mixed models were used to compare the reduction in BP and FPG level from baseline to week 8 of the treatment and the difference among the three treatment groups, adjusting for pertinent covariates. Results Four hundred forty-three subjects (57.3% women, 27–75 y of age) successfully completed the trial. After the 8-wk treatment, compared with baseline, all treatment groups showed significant reduction of BP but not of FPG. There was no significant difference in BP or FPG reduction among the three treatment groups. In subgroup analysis, we found that in subjects with hyperglycemia (FPG ≥6.1 mmol/L) at baseline, FPG reduction was significantly greater in the high-FA group (−0.80 ± 1.20 mmol/L) than in the low-FA group (−0.39 ± 1.44 mmol/L) and the control group (−0.23 ± 1.30 mmol/L). Regression analysis further confirmed that FPG reduction in the high-FA group was −0.68 ± 0.28 mmol/L greater than in the control group (P = 0.015), even after adjustment for important covariates. A dose–response trend was evident (P for trend = 0.025) and the test for an interaction between treatment group and baseline FPG was significant (P Conclusion In this sample of adult Chinese hypertensive patients, FA combined with enalapril showed a greater beneficial effect on reduction of FPG in a dose-related fashion than did enalapril alone among subjects with hyperglycemia.

In the present study, we aimed to establish a rabbit atherosclerosis model and examine atherosclerotic plaques by using optical coherence tomography (OCT) and intravascular ultrasonography (IVUS) to evaluate the clinical usefulness of these diagnostic tools in the detection of atherosclerotic plaques. Twenty healthy New Zealand rabbits were fed on a high-fat diet for 4 weeks and then subjected to abdominal aortic intimal injury. The OCT and IVUS were performed after 8 weeks. The distal and proximal plaque images were marked to observe the plaque thickness and features of the lesions at the tunica intima and tunica media. Moreover, a pathological examination was performed to evaluate the efficacies of OCT and IVUS. The mean (SD) plaque thickness on OCT and IVUS images was 386.5 (125.3) μm and 412.7 (165.8) μm, respectively. Pathological examinations indicated a mean (SD) plaque thickness of 360.2 (98.l) μm (P > 0.05). No significant differences were noted between the 2 methods. The intimal and medial thickness measured with OCT showed greater correlation with pathologically measured thickness (r = 0.95, P < 0.001 for OCT; r = 0.88, P < 0.001 for IVUS); in particular, the intimal thickness measurements on OCT showed a higher correlation (r = 0.98, P < 0.001). However, the measurements obtained using IVUS were not accurate. Thus, compared with IVUS, OCT was more accurate in determining the nature and thickness of vascular plaques.

Several studies have found that body adiposity index (BAI) is a better index of body adiposity than body mass index (BMI) in African and Mexican American adults. This study aims to evaluate the ability of BAI to predict body adiposity in Chinese children and adults.In total, 2425 children and 5726 adults were recruited from rural China. All participants completed whole-body dual-energy X-ray absorptiometry (DXA) and anthropometric measures. The correlation of BMI, BAI, and waist circumference (WC) to DXA adiposity indexes was performed across sex-specific adult and age- and sex-specific child cohorts, using Spearman correlation and linear regression models, respectively.Both BMI and WC had a higher correlation with all adiposity indexes (whole body fat, percent body fat [Bfat%], trunk fat, and percent trunk fat [Tfat%]) measured by DXA than did BAI in both adults and children. Meanwhile, most of the linear regression model associations for BMI with Bfat% and Tfat% had a greater adjusted R(2) than those for BAI among both children and adults.This study indicates that BMI and WC are better tools than BAI for estimating whole body fat and central body fat in a Chinese population.

Objective The controversy that iodized salt may increase the risk of thyroid disorders has been aroused in China during the past decade. Most of studies focused on adult rather than children. We aimed to explore whether iodized salt was associated with an increased risk of thyroid nodule in Chinese children. Methods The cross-sectional study was conducted in Hangzhou, China, in 2010. Iodized salt intake, urine iodine concentration (UIC) and thyroid nodule (by ultrasonography) were measured in 3026 children. The associations of iodized salt with thyroid nodule were evaluated using multiple logistic regression models. Results The prevalence of thyroid nodule was 10.59% among Chinese children. Girls (11.89%) had higher prevalence of thyroid nodule than boys (9.26%). No significant association was observed between type of salt and thyroid nodule in pooled samples, boys and girls, respectively. Similar associations were observed between UIC and thyroid nodule. There was no significant association between milk consumption and thyroid nodule as well. Conclusion The present study indicated that non-iodized salt may not increase the risk of thyroid nodules among Chinese children. Similar associations were observed between milk consumption, UIC and thyroid nodules.

Background Exposure to electromagnetic field (EMF) emitted by mobile phone and other machineries concerns half the world's population and raises the problem of their impact on human health. The present study aims to explore the effects of electromagnetic field exposures on sleep quality and sleep duration among workers from electric power plant. Methods A cross-sectional study was conducted in an electric power plant of Zhejiang Province, China. A total of 854 participants were included in the final analysis. The detailed information of participants was obtained by trained investigators using a structured questionnaire, which including socio-demographic characteristics, lifestyle variables, sleep variables and electromagnetic exposures. Physical examination and venous blood collection were also carried out for every study subject. Results After grouping daily occupational electromagnetic exposure into three categories, subjects with long daily exposure time had a significantly higher risk of poor sleep quality in comparison to those with short daily exposure time. The adjusted odds ratios were 1.68 (95%CI: 1.18, 2.39) and 1.57 (95%CI: 1.10, 2.24) across tertiles. Additionally, among the subjects with long-term occupational exposure, the longer daily occupational exposure time apparently increased the risk of poor sleep quality (OR (95%CI): 2.12 (1.23∼3.66) in the second tertile; 1.83 (1.07∼3.15) in the third tertile). There was no significant association of long-term occupational exposure duration, monthly electric fee or years of mobile-phone use with sleep quality or sleep duration. Conclusions The findings showed that daily occupational EMF exposure was positively associated with poor sleep quality. It implies EMF exposure may damage human sleep quality rather than sleep duration.

Background: The controversy that iodized salt may increase the risk of thyroid disorders has arisen in China during the past several years. Objective: This study aimed to explore whether iodized salt increased the risk of thyroid nodule among a Chinese population. Design: A cross-sectional study was conducted in Hangzhou, China, in 2010. Iodized salt intake, urinary iodine concentration (UIC), and thyroid nodule (by ultrasonography) were measured in 9412 adults. The associations of iodized salt with thyroid nodule were evaluated by using multiple mixed logistic regression models. Results: The prevalence of thyroid nodule among men and women was 24.1% and 34.7%, respectively. Adults consuming noniodized salt had an increased risk of thyroid nodule (OR: 1.36; 95% CI: 1.01, 1.83). Similarly, compared with moderate salt appetite, mild salt appetite was associated with an increased risk of thyroid nodule among all adults (OR: 1.19; 95% CI: 1.03, 1.37) and among women (OR: 1.23; 95% CI: 1.03, 1.46). Furthermore, those who consumed neither iodized salt nor milk had a higher risk of thyroid nodule (OR: 1.72; 95% CI: 1.21, 2.43) than did those who consumed both iodized salt and milk. In addition, an increased risk of thyroid nodule (OR: 1.25; 95% CI: 1.07, 1.45) was observed among both pooled samples and women with low UIC. Conclusions: These findings indicate that low iodine intake may increase the risk of thyroid nodule in a Chinese population, particularly in women. Hence, the Universal Salt Iodization program may be indispensable for a coastal Chinese population such as that living in Hangzhou. This trial was registered at clinicaltrials.gov as NCT01838629. Am J Clin Nutr doi: 10.3945/ajcn.112.054353.

The primary aim was to respectively evaluate PLA2G4A mutants modifying protective effect of tea consumption against colorectal cancer (CRC), colon and rectal cancer.All participants were recruited from January 2006 to April 2008. The information about tea consumption was collected by a structured questionnaire. CRC patients were diagnosed based on histology. Four single-nuclear polymorphisms (SNPs) in PLA2G4A gene were selected. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC, colon and rectal cancer.Three hundred patients with CRC and 296 controls well-matched were used in the final analyses. The significant individual associations between four SNPs (rs6666834, rs10911933, rs4650708 and rs7526089) and CRC were not observed. However, their CTAC haplotype was significantly associated with the increased risk of CRC (OR = 3.06; 95%CI = 1.52-6.19), compared with TCAC haplotype. Drinking tea was correlated with a decreased risk of CRC after adjustment for covariates (OR = 0.61; 95%CI = 0.39-0.97). Meanwhile, compared with no-tea drinkers with TT/CT genotype of rs6666834, tea drinkers with TT/CT or CC had significant lower risk of CRC (OR = 0.6, 95%CI = 0.36-1.00 for TT/CT; 0.38, 0.19-0.74 for CC). The joint effects between the remaining three SNPs and drinking tea on CRC were observed as well. Similar findings were observed on colon and rectal cancers.Tea consumption and haplotype of mutants in PLA2G4A gene were respectively associated with the risk of CRC. PLA2G4A mutants modified the protective effect of tea consumption against CRC, colon and rectal cancers in Chinese population.

We examined the tracking of blood glucose, the development of prediabetes, and estimated their genetic contributions in a prospective, healthy, rural Chinese twin cohort. This report includes 1,766 subjects (998 males, 768 females) aged 6-21 years at baseline who completed a 6-year follow-up study. Oral glucose tolerance test was performed for all subjects at both baseline and follow-up. We found that subjects with low fasting plasma glucose (FPG) or 2 h post-load glucose (PG) levels at baseline tended to remain at the low level at follow-up. Subjects in the top tertile of baseline plasma glucose tended to have a higher risk of developing prediabetes at follow-up compared to the low tertile: in males, 37.6% vs. 27.6% for FPG and 37.2% vs. 25.7% for 2hPG, respectively; in females, 31.0% vs. 15.4% for FPG and 28.9% vs. 15.1% for 2 h PG, respectively. Genetic factors explained 43% and 41% of the variance of FPG, and 72% and 47% for impaired fasting glucose for males and females, respectively; environmental factors substantially contribute to 2hPG status and impaired glucose tolerance. In conclusion, in this cohort of healthy rural Chinese children and adolescents, we demonstrated that both FPG and 2hPG tracked well and was a strong predictor of prediabetes. The high proportion of children with top tertile of blood glucose progressed to prediabetes, and the incidence of prediabetes has a male predominance. Genetic factors play more important role in fasting than postload status, most of which was explained by unique environmental factors.

The aim of this study is to investigate the relationship between sleep duration and body composition and to estimate the genetic contribution of sleep duration and body composition in a Chinese twin population. This cross-sectional analysis included 738 men and 511 women aged 21–72 year. Anthropometric and dual-energy X-ray absorptiometry (DXA) measures of body composition were used. Sleep duration was obtained from a standard sleep questionnaire. Multiple regression models were used to examine the association between sleep duration and body composition measures. Structural equation modeling was used to assess the heritability of sleep duration and body composition. Compared with individuals in the 2nd and 3rd age-specific quartiles of sleep duration (reference group), shorter (1st quartile) sleep duration among women but not men was associated with higher z-scores (0.248–0.317) for all adiposity measures—BMI, fat mass index (FMI), percent body fat mass (%BF), and percent trunk fat mass (%TF), P < 0.05 for each—and with 0.306 lower z-scores for percent body lean mass (%LM) and 0.353 lower lean/fat mass ratio (LFR), P < 0.01 for each. The heritability of sleep duration was 0.27 in men and 0.29 in women, while the heritability of body composition was as high as 0.56–0.73 after adjustment for age in both genders. Short sleep duration was associated with increased body fat and decreased lean body mass in women but not in men. Sleep duration was largely influenced by environmental factors while adiposity measures were mainly influenced by genetic factors.

Context: Elevated C-reactive protein (CRP) is a marker of cardiovascular risk in adults. Patterns and determinants of CRP in adolescents have not been well described. Objective: This study aimed to determine how CRP varies by age, gender, Tanner stage, and body fat composition in rural Chinese adolescents and to what degree adiposity-CRP associations are attributable to shared genetic and environmental factors. Design and Setting: Data were derived from an ongoing study of metabolic syndrome in a large community-based twin cohort enrolled in Anqing, China. Participants: The study sample included 1180 adolescent twins aged 13–21 yr. Main Outcome Measures: Plasma CRP concentrations were measured by sandwich immunoassay using flow metric xMAP technology. Body fat composition was assessed by dual-energy x-ray absorptiometry. Results: CRP levels linearly increased across age and Tanner stage in males (P ≤ 0.0001), but in females, CRP exhibited no trend after adjusting for fat mass (P > 0.05). For males, the most explanatory measure was body mass index (partial r2 = 5.2%), whereas percent body fat (partial r2 = 8.8%) was more explanatory in females. Of the phenotypic correlations between adiposity measures and CRP (0.25–0.28), 86–89% were attributed to shared genetic factors and 11–14% to common unique environmental factors in both sexes. Conclusions: Adiposity is a strong determinant of CRP even in this relatively lean Chinese population. There is notable gender difference for the CRP pattern and the relationship of CRP with adiposity during adolescence. To a large degree, common genetic factors may underlie the observed adiposity-CRP-phenotypic correlations.

ObjectiveThis study investigated the associations of plasma leptin levels with insulin resistance (IR) and prediabetes in relatively lean, rural Chinese men and women.Design and methodsThis study included 574 subjects aged 21–45 years from a community-based twin cohort. Plasma leptin concentrations were measured by sandwich immunoassays using flowmetric xMAP technology. Prediabetes was defined based on fasting plasma glucose and 75-g oral glucose tolerance test. Multivariate linear and logistic regression analyses were used to investigate gender-specific associations of leptin with IR measures and prediabetes, adjusting for intra-twin correlation, measures of adiposity, and other pertinent covariates.ResultsThe body mass index is 22.3±2.7 kg/m2 in men and 22.5±2.7 kg/m2 in women. Leptin levels were positively associated with IR. Individuals with higher tertiles of leptin also had increased risk of prediabetes with odds ratios (OR) of 2.6 (95% confidence interval (CI): 1.4–5.1) and 4.3 (95% CI: 2.1–8.7) in men; OR of 1.1 (95% CI: 0.6–2.1) and 3.1 (95% CI 1.5–6.2) in women for second and third tertile respectively. These associations were attenuated after further adjusting for adiposity measurements only in men. The leptin–prediabetes associations disappeared after adjusting for the homeostatic model assessment of IR in both genders.ConclusionIn this sample of relatively lean rural Chinese adults, plasma leptin levels were associated with IR and prediabetes in a dose–response fashion, which were not totally explained by adiposity. Our data emphasize that prediabetes is not all about obesity, and leptin may be an additional biomarker for screening individuals at high risk for prediabetes in this population.

This study was an attempt to examine the phenotypic, genetic, and environmental correlations between percent fat mass (PFM) and bone parameters, especially hip geometry, among 786 males and 618 females aged 13 to 21 years from a Chinese twin cohort. PFM, bone area (BA), bone mineral content (BMC), cross-sectional area (CSA), and section modulus (SM) were obtained by dual-energy X-ray absorptiometry. Multiple linear regression models were used to assess the PFM-bone relationships. A structural equation model for twin design was used to estimate genetic/environmental influences on individual phenotype and phenotypic correlations. After controlling for body weight and other pertinent covariates, we observed inverse associations between PFM and bone parameters: Compared with the lowest age- and gender-specific tertile of PFM, males in the highest tertile of PFM had lower measures of whole-body-less-head BA (WB-BA), lumbar spine BA (L2–L4-BA), total-hip BA (TH-BA), total-hip BMC, CSA, and SM (p < .005 for all, adjusted p < .05). Similar inverse associations were observed in females for all the preceding parameters except WB-BA and L2–L4-BA. These associations did not vary significantly by Tanner stages. In both genders, the estimated heritabilities were 80% to 86% for BMC, 67% to 80% for BA, 74% to 77% for CSA, and 64% for SM. Both shared genetics and environmental factors contributed to the inverse PFM-bone correlations. We conclude that in this sample of relatively lean Chinese adolescents, at a given body weight, PFM is inversely associated with BA, BMC, and hip geometry in both genders, and such associations are attributed to both shared genetic and environmental factors. © 2010 American Society for Bone and Mineral Research.

Context: There is evidence that leptin is involved in the etiology of obesity-related cardiovascular disease in adults. This raises the question of whether leptin levels in adolescence are indicative of adiposity-related cardiovascular risk. Objective: This study investigated gender-specific patterns of plasma leptin during adolescence, assessed which adiposity measurements are most strongly associated with plasma leptin, and estimated to what degree leptin-adiposity associations are influenced by genetic factors. Methods: Plasma leptin concentrations were determined using a sandwich immunoassay. Associations between plasma leptin and several adiposity measurements were examined using generalized estimating equations. Genetic contribution to leptin-adiposity association was estimated by Cholesky decomposition models using twin design. Results: Plasma leptin levels were higher in females than males at all Tanner stages. In females, body mass index, waist circumference, fat mass index (FMI), and percentage body fat (%BF) had similar associations with leptin levels. In males, %BF and FMI were more strongly associated with leptin levels than body mass index and waist circumference. In both males and females, percentage trunk fat had the weakest association with leptin among the five adiposity measures. Shared genetic factors account for more than 80% of the phenotypic correlation between %BF and leptin. Conclusions: We found gender differences in leptin levels and leptin-adiposity associations. In both genders, leptin levels were strongly associated with %BF and FMI, particularly in males. Shared genetic factors contributed largely to the phenotypic correlation between leptin and %BF. Our findings underscored the importance of further investigation of leptin as a biomarker of adiposity in adolescents.

Obesity and allergic diseases have increased dramatically in recent decades. Although adiposity has been associated with asthma, associations with allergic sensitization have been inconsistent.To examine the association of adiposity and lipid profiles with allergic sensitization.This study included 1187 rural Chinese twins (653 men) age 18 to 39 years, with skin prick tests, anthropometric and dual-energy x-ray absorptiometry-assessed adiposity measures, and lipid assessments. Allergic sensitization was defined as positive SPT to/=1 allergen (9 foods and 5 aeroallergens tested). We applied sex-stratified generalized estimating equations to assess the association of adiposity and serum lipids with allergic sensitization, and structural equation models to estimate the genetic/environmental influences on any observed associations.Men had lower percent body fat (% BF) (13.9% vs. 28.8%) but higher rates of allergic sensitization (56.2% vs 36.7%) than women. Men in the highest %BF quartile were 2.1 times more likely to be sensitized than the lowest quartile (95% CI, 1.3-3.5; P trend = .003). In men, the risk of allergic sensitization increased with high-density lipoprotein (HDL)40 mg/dL (odds ratio = 4.0; 95% CI, 1.8-9.2) and higher low-density lipoprotein quartiles (P trend = .007). This appeared to be partially explained by shared genetic factors between serum lipid levels and allergic sensitization. In females, lower HDL was associated with increased risk of allergic sensitization.In this relatively lean Chinese population, higher %BF, lower HDL and higher LDL were associated with greater risk of allergic sensitization, most notable in men. The observed associations among adiposity, serum lipids, and allergic sensitization in men appear to be partially explained by common genetic influences on these traits.

Background The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend might be associated with lifestyle and urbanization. Objective We sought to describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population. Methods The data were derived from a community-based twin study in Anqing, China. Skin prick tests were performed to foods and aeroallergens. Atopy was defined as sensitization to 1 or more allergens. Allergic disease was ascertained by means of self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs. Results Of 2118 subjects, 57.6% were male (n = 1220). Ages ranged from 11 to 71 years, and 43.3% were children (n = 918). Atopy was observed in 47.2% (n = 999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed that risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be less than 1%. Conclusions Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low.

Objective Previous studies have found that overweight and obesity are related to numerous diseases, including thyroid cancer and thyroid volume. This study evaluates the relationship between body size and the presence of thyroid nodules in a Chinese population. Methods A total of 6793 adults and 2410 children who underwent thyroid ultrasonography were recruited in this cross-sectional study in Hangzhou, Zhejiang Province, China, from March to October, 2010. Sociodemographic characteristics and potential risk factors of thyroid nodules were collected by questionnaire. Height and weight were measured using standard protocols. Associations of height, weight, body mass index (BMI) and body surface area (BSA) with the presence of thyroid nodules were evaluated using multiple logistic regression models. Results After adjustment for potential risk factors, an increased risk of thyroid nodule incidence was associated with height (OR 1.15, 95% CI 1.02 to 1.30), weight (OR 1.40, 95% CI 1.24 to 1.58), BMI (OR 1.26, 95% CI 1.11 to 1.42) and BSA (OR 1.43, 95% CI 1.27 to 1.62) in all adults, but most obviously in women. In children, similar associations were observed between risk of thyroid nodule incidence and weight, BMI and BSA, but not height. BSA was the measurement most significantly associated with thyroid nodules in both adults and children. Conclusions This study identified that the presence of thyroid nodules was positively associated with weight, height, BMI and BSA in both women and girls. It suggests that tall, obese individuals have increased susceptibility to thyroid nodules. Trial registration number: NCT01838629.

Individual variations in the pharmacokinetics and pharmacodynamics of antihypertensive drugs are influenced by genetic and environmental factors. The ANP gene, which encodes the precursor of atrial natriuretic peptide (ANP), is among the candidate genes for genetic susceptibility to hypertension.This study examined the relationship between ANP Val7Met polymorphism (Single Nucleotide Polymorphism database ID: rs5063) and baseline blood pressure (BP), plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension.Patients with essential hypertension who had taken no antihypertensive medications within 4 weeks of study initiation received oral irbesartan 150 mg/d for 4 weeks. Genotyping was performed for all patients. BP was measured before dosing on the 1st and 28th days of treatment. Plasma irbesartan concentrations were measured using high-performance liquid chromatography with fluorescent detection. Antihypertensive efficacy was defined as attainment of a diastolic BP (DBP)90 mm Hg (DBP analysis), a systolic BP (SBP)140 mm Hg (SBP analysis), and a DBP90 mm Hg and SBP140 mm Hg (DBP and SBP analysis).The study included 756 patients, 621 with the Val/Val genotype and 135 with the Val/Met+Met/Met genotypes. There were no significant differences in age, body mass index, sex, education level, occupation, alcohol consumption, or smoking status between the 2 groups. Patients with the Val/Met+Met/Met genotypes had a significantly lower mean baseline DBP compared with those with the Val/Val genotype (adjusted regression coefficient [SE]: -2.5 [1.0] mm Hg; P = 0.012) and significantly lower mean steady-state plasma trough irbesartan concentrations (adjusted regression coefficient: -12.6 [4.1]; P = 0.002). No significant association was found between antihypertensive efficacy and Val7Met polymorphism in the overall population, but in an analysis by baseline DBP status, patients with the Val/Met+Met/Met genotype a baseline DBPor =100 mm Hg had significantly smaller reductions in DBP (adjusted regression coefficient: -5.7 [1.4] mm Hg; P0.001) and SBP compared with those with the Val/Val genotype and a baseline DBPor =100 mm Hg (adjusted regression coefficient: -9.8 [2.9] mm Hg; P0.001).The findings of this study suggest that in these rural Chinese patients with essential hypertension, ANP Val7Met polymorphism may be a genetic marker for baseline DBP, plasma irbesartan concentrations, and the antihypertensive efficacy of short-term irbesartan therapy.

Objective This study aims to evaluate perceived lifetime stress, perceived stress during pregnancy, chronic hypertension, and their joint association with preeclampsia risk. Study Design This study includes 4314 women who delivered a singleton live birth at the Boston Medical Center from October 1998 through February 2008. Chronic hypertension was defined as hypertension diagnosed before pregnancy. Information regarding lifetime stress and perceived stress during pregnancy was collected by questionnaire. Preeclampsia was diagnosed by clinical criteria. Results Lifetime stress (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.6–2.9), perceived stress during pregnancy (OR, 1.7; 95% CI, 1.3–2.2), and chronic hypertension (OR, 10.4; 95% CI, 7.5–14.4) were each associated with an increased risk of preeclampsia. Compared to normotensive pregnancy with low lifetime stress, both normotensive pregnancy with high lifetime stress (OR, 2.1; 95% CI, 1.6–2.9) and pregnancy with chronic hypertension and low lifetime stress (OR, 10.2; 95% CI, 7.0–14.9) showed an increased risk of preeclampsia, while pregnancy with high lifetime stress and chronic hypertension yielded the highest risk of preeclampsia (OR, 21.3; 95% CI, 10.2–44.3). The joint association of perceived stress during pregnancy and chronic hypertension with preeclampsia was very similar to that of the joint association of lifetime stress and chronic hypertension with preeclampsia. Conclusion This finding indicates that high psychosocial stress and chronic hypertension can act in combination to increase the risk of preeclampsia up to 20-fold. This finding underscores the importance of efforts to prevent, screen, and manage chronic hypertension, along with those to reduce psychosocial stress, particularly among women with chronic hypertension.

Objective In the United States, the rate of preterm delivery (PTD) is higher in African Americans (17.8%) than non-Hispanic whites (11.5%). Such disparity cannot be fully explained by differences in socioenvironmental factors. Study Design We genotyped 812 mothers in a case-control PTD study at Boston Medical Center who self-reported their ethnicity as “black.” Regression analysis and Wilcoxon rank-sum test were applied to evaluate ancestral distribution and the association between genetic ancestry and PTD-related traits, as well as the potential confounding effect of population stratification. Results The estimated African ancestral proportion was 0.90 ± 0.13. We found significant associations of ancestral proportion with PTD as a whole and PTD subgrouped by the presence of maternal hypertensive disorders. We did not observe significant confounding as a result of population stratification in this case-control PTD study. Conclusion Our data underline the need for more intensive investigation of genetic admixture in African Americans to identify novel susceptibility genes of PTD.