Browsing by Author "Wang, Huan"

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    BMI, leisure-time physical activity, and physical fitness in adults in China: results from a series of national surveys, 2000–14
    (Elsevier, 2016-06) Tian, Ye; Jiang, Chongmin; Wang, Mei; Cai, Rui; Zhang, Yanfeng; He, Zihong; Wang, Huan; Wu, Dongming; Wang, Fubaihui; Tang, Qiang; Yang, Yang; Zhao, Jin; Lv, Shaojun; Zhou, Weihai; Yu, Bo; Lan, Jiang; Yang, Xinping; Zhang, Linxia; Tian, Hui; Gu, Zhuangzhuang; Song, Yiqing; Huang, Tianyi; McNaughton, Lars R.; Department of Epidemiology, Richard M. Fairbanks School of Public Health
    Background Obesity, physical inactivity, and reduced physical fitness contribute to the rising burden of chronic diseases in China. We investigated these factors in Chinese adults over a 14-year period (2000–14) using data from randomised national surveys. Methods We did four national surveys in 2000, 2005, 2010, and 2014 among Chinese adults aged 20–59 years. We used BMI to assess underweight (<18·5 kg/m2), overweight (≥23·0 to <27·5 kg/m2), and obesity (≥27·5 kg/m2). Central obesity was defined as a waist circumference greater than 90 cm in men and greater than 85 cm in women. We assessed leisure-time physical activity (LTPA) by whether or not participants had completed the recommended minimum 150 min of moderate or 75 min of vigorous exercise per week. Indices for assessment of physical fitness were forced vital capacity, resting heart rate, hand grip strength, sit and reach distance, and time standing on one leg. Findings 151 656 (78%) of 193 440 adults responded to the survey in 2000, 163 386 (84%) in 2005, 154 931 (80%) in 2010, and 146 703 (76%) in 2014. The prevalence of obesity increased from 8·6% in 2000, to 10·3% in 2005, 12·2% in 2010, and 12·9% in 2014 (estimated increase 0·32% per year, 95% CI 0·30–0·33; p<0·0001). The equivalent estimates were 37·4%, 39·2%, 40·7%, and 41·2% for overweight (estimated increase 0·27% per year, 95% CI 0·25–0·30; p<0·0001) and 13·9%, 18·3%, 22·1%, and 24·9% for central obesity (estimated increase 0·78% per year, 0·76–0·80; p<0·0001). The prevalence of overweight, obesity, and central obesity increased with age (all p<0·0001) and was higher in men than in women (all p<0·0001). We noted a simultaneous decrease in the prevalence of underweight (estimated decrease of 0·06% per year, 95% CI 0·04–0·07; p<0·0001). The proportion of adults meeting the minimum LTPA recommendation increased over time (17·2% in 2000, 18·1% in 2005, and 22·8% in 2014), with the estimated prevalence change per year being 0·33% (95% CI 0·24–0·42; p<0·0001) for underweight people, 0·50% (0·47–0·53; p<0·0001) for normal-weight people, 0·37% (0·34–0·40; p<0·0001) for overweight people, and 0·06% (0·00–0·13; p=0·044) for obese people. We noted deteriorations over time in all measures of physical fitness in normal-weight adults (all p<0·0001), apart from resting heart rate (p=0·69). Interpretation Despite increased participation in LTPA, we noted increases in overweight or obesity and a decrease in physical fitness in Chinese adults. Continued nationwide interventions are needed to promote physical activity and other healthy lifestyle behaviours in China.
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    Leptospiral Hemolysins Induce Proinflammatory Cytokines through Toll-Like Receptor 2-and 4-Mediated JNK and NF-κB Signaling Pathways
    (Public Library of Science, 2012) Wang, Huan; Wu, Yifei; Ojcius, David M.; Yang, X. Frank; Zhang, Chenglin; Ding, Shibiao; Lin, Xu’ai; Yan, Jie; Microbiology and Immunology, School of Medicine
    Background: Infection with pathogenic Leptospira species causes serious systemic inflammation in patients. Although a few leptospiral proinflammatory molecules have been identified, Leptospira likely encodes other unidentified strong inflammation stimulators. The pathogenic L. interrogans genome encodes numerous putative hemolysin genes. Since hemolysins from other bacteria can cause inflammatory reactions, we hypothesized that leptospiral hemolysins may function as proinflammatory stimulators that contribute to the strong inflammation associated with Leptospira infection. Methodology/principal findings: We first used cytokine protein microarrays for systematic analysis of serum cytokine profiles in leptospirosis patients and leptospire-infected mice. We found that IL-1β, IL-6 and TNF-α were the main proinflammatory cytokines in the sera of both the patients and the mice. We then analyzed eight putative hemolysins in L. interrogans strain Lai. The results showed that five of them, Sph1, Sph2, Sph3, HlpA and TlyA were secreted and had hemolytic activity. More importantly, these five hemolysins induced the strong production of IL-1β, IL-6 and TNF-α in human and mouse macrophages (although a bit lower in the latter). Furthermore, blockade of TLR2 or TLR4 with either antibodies or inhibitors of the NF-κB or JNK signaling pathways significantly reduced the production of hemolysin-induced IL-1β, IL-6 and TNF-α. Macrophages isolated from TLR2-, TLR4-or double TLR2-and 4-deficient mice also confirmed that the leptospiral hemolysins that induce proinflammatory cytokines are both TLR2-and TLR4-dependent. Conclusions/significance: Our findings demonstrate that L. interrogans secretes many hemolysins that function as powerful inducers of proinflammatory cytokines through both TLR2-and TLR4-dependent JNK and NF-κB pathways.
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    Phase II Clinical and Translational Study of Everolimus ± Paclitaxel as First-Line Therapy in Cisplatin-Ineligible Advanced Urothelial Carcinoma
    (Oxford University Press, 2022) Jun, Tomi; Hahn, Noah M.; Sonpavde, Guru; Albany, Constantine; MacVicar, Gary R.; Hauke, Ralph; Fleming, Mark; Gourdin, Theodore; Jana, Bagi; Oh, William K.; Taik, Patricia; Wang, Huan; Ramakrishnan Varadarajan, Ajay; Uzilov, Andrew; Galsky, Matthew D.; Medicine, School of Medicine
    Background: Treatment options have been historically limited for cisplatin-ineligible patients with advanced urothelial carcinoma (UC). Given the need for alternatives to platinum-based chemotherapy, including non-chemotherapy regimens for patients with both impaired renal function and borderline functional status, in 2010 (prior to the immune checkpoint blockade era in metastatic UC), we initiated a phase II trial to test the activity of everolimus or everolimus plus paclitaxel in the cisplatin-ineligible setting. Methods: This was an open-label phase II trial conducted within the US-based Hoosier Cancer Research Network (ClinicalTrials.gov number: NCT01215136). Patients who were cisplatin-ineligible with previously untreated advanced UC were enrolled. Patients with both impaired renal function and poor performance status were enrolled into cohort 1; patients with either were enrolled into cohort 2. Patients received everolimus 10 mg daily alone (cohort 1) or with paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 28-day cycle (cohort 2). The primary outcome was clinical benefit at 4 months. Secondary outcomes were adverse events, progression-free survival (PFS), and 1-year overall survival (OS). Exploratory endpoints included genomic correlates of outcomes. The trial was not designed for comparison between cohorts. Results: A total of 36 patients were enrolled from 2010 to 2018 (cohort 1, N = 7; cohort 2, N = 29); the trial was terminated due to slow accrual. Clinical benefit at 4 months was attained by 0 (0%, 95% confidence interval [CI] 0-41.0%) patients in cohort 1 and 11 patients (37.9%, 95% CI 20.7-57.7%) in cohort 2. Median PFS was 2.33 (95% CI 1.81-Inf) months in cohort 1 and 5.85 (95% CI 2.99-8.61) months in cohort 2. Treatment was discontinued due to adverse events for 2 patients (29%) in cohort 1 and 11 patients (38%) in cohort 2. Molecular alterations in microtubule associated genes may be associated with treatment benefit but this requires further testing. Conclusion: Everolimus plus paclitaxel demonstrates clinical activity in cisplatin-ineligible patients with metastatic UC, although the specific contribution of everolimus cannot be delineated. Patients with both impaired renal function and borderline functional status may be difficult to enroll to prospective trials.