[Effects of propiconazole on physiological and biochemical properties of Panax notoginseng and dietary risk assessment].

To study the residue and dietary risk of propiconazole in Panax notoginseng and the effects on physiological and bioche-mical properties of P. notoginseng, we conducted foliar spraying of propiconazole on P. notoginseng in pot experiments. The physiolo-gical and biochemical properties studied included leaf damage, osmoregulatory substance content, antioxidant enzyme system, non-enzymatic system, and saponin content in the main root. The results showed that at the same application concentration, the residual amount of propiconazole in each part of P. notoginseng increased with the increase in the times of application and decreased with the extension of harvest interval. After one-time application of propiconazole according to the recommended dose(132 g·hm~(-2)) for P. ginseng, the half-life was 11.37-13.67 days. After 1-2 times of application in P. notoginseng, propiconazole had a low risk of dietary intake and safety threat to the population. The propiconazole treatment at the recommended concentration and above significantly increased the malondialdehyde(MDA) content, relative conductivity, and osmoregulatory substances and caused the accumulation of reactive oxygen species in P. notoginseng leaves. The propiconazole treatment at half(66 g·hm~(-2)) of the recommended dose for P. ginseng significantly increased the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) in P. notoginseng leaves. The propiconazole treatment at 132 g·hm~(-2) above inhibited the activities of glutathione reductase(GR) and glutathione S-transferase(GST), thereby reducing glutathione(GSH) content. Proconazole treatment changed the proportion of 5 main saponins in the main root of P. notoginseng. The treatment with 66 g·hm~(-2) propiconazole promoted the accumulation of saponins, while that with 132 g·hm~(-2) and above propiconazole significantly inhibited the accumulation of saponins. In summary, using propiconazole at 132 g·hm~(-2) to prevent and treat P. notoginseng diseases will cause stress on P. notoginseng, while propiconazole treatment at 66 g·hm~(-2) will not cause stress on P. notoginseng but promote the accumulation of saponins. The effect of propiconazole on P. notoginseng diseases remains to be studied.

Rapid determination and dietary intake risk assessment of 249 pesticide residues in Panax notoginseng.

UPLC-MS/MS and GC-MS/MS were used to establish a method to simultaneously determine various pesticide residues in Panax notoginseng. Results showed that the limits of detection of 249 pesticides were all 5-10 µg/kg. The detection rate of pesticides in 121 P. notoginseng samples was 93.39%, and 19 pesticides were detected. According to the US Code of Federal Regulations, the Chinese Pharmacopoeia recommended algorithm, and the Japanese "positive list system", the pass rates of pesticide residues were 100%, 99.17%, and 89.26%, respectively. The chronic risk quotient (ADI%) and acute risk quotient (ARfD%) of P. notoginseng were 0.00-0.12% and 0.00-0.15%, respectively. In summary, the detection method established in this study can be used for routine analysis of various P. notoginseng pesticide residues. The pesticide residues in the main root samples of P. notoginseng were at a safe level and unlikely pose health risks to consumers.

Assessment of the Potential for Veverimer Drug-Drug Interactions.

Veverimer is a polymer being developed as a potential treatment of metabolic acidosis in patients with chronic kidney disease. Veverimer selectively binds and removes hydrochloric acid from the gastrointestinal tract, resulting in an increase in serum bicarbonate. Veverimer is not systemically absorbed, so potential drug-drug interactions (DDIs) are limited to effects on the absorption of other oral drugs through binding to veverimer in the gastrointestinal tract or increases in gastric pH caused by veverimer binding to hydrochloric acid. In in vitro binding experiments using a panel of 16 test drugs, no positively charged, neutral, or zwitterionic drugs bound to veverimer. Three negatively charged drugs (furosemide, aspirin, ethacrynic acid) bound to veverimer; however, this binding was reduced or eliminated in the presence of normal physiologic concentrations (100-170 mM) of chloride. Veverimer increased gastric pH in vivo by 1.5-3 pH units. This pH elevation peaked within 1 hour and had returned to baseline after 1.5-3 hours. Omeprazole did not alter the effect of veverimer on gastric pH. The clinical relevance of in vitro binding and the transient increase in gastric pH was evaluated in human DDI studies using two drugs with the most binding to veverimer (furosemide, aspirin) and two additional drugs with pH-dependent solubility effecting absorption (dabigatran, warfarin). None of the four drugs showed clinically meaningful DDI with veverimer in human studies. Based on the physicochemical characteristics of veverimer and results from in vitro and human studies, veverimer is unlikely to have significant DDIs. SIGNIFICANCE STATEMENT: Patients with chronic kidney disease, who are usually on many drugs, are vulnerable to drug-drug interactions (DDIs). The potential for DDIs with veverimer was evaluated based on the known site of action and physicochemical structure of the polymer, which restricts the compound to the gastrointestinal tract. Based on the findings from in vitro and human studies, we conclude that veverimer is unlikely to have clinically significant DDIs.

DEFB1 rs11362 Polymorphism and Risk of Chronic Periodontitis: A Meta-Analysis of Unadjusted and Adjusted Data.

Objective: Chronic periodontitis (CP) is a growing problem that affects the worldwide population, having significant impacts on people's daily lives and economic development. Genetics is an important component in the determination of individual susceptibility to periodontal diseases. Numerous studies have been performed to investigate the association between beta defensin 1 (DEFB1) rs11362 polymorphism and risk of CP, but the results are still inconclusive. Therefore, we conducted this meta-analysis to ascertain whether this variation in DEFB1 is associated with CP susceptibility. Methods: The relevant studies were searched in PubMed and Chinese National Knowledge Infrastructure (CNKI) databases up to January 9, 2018. Two independent authors selected citations and extracted the data from eligible studies. Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were used to assess the strength of the association. Results: Seven case-control studies were included in this meta-analysis. Based on unadjusted data, there was no obvious association between DEFB1 rs11362 polymorphism and CP risk in all genetic models (A vs. G: OR = 0.86, 95%CI = 0.61-1.20; AA vs. GG: OR = 0.83, 95% CI = 00.50-1.39; AG vs. GG: OR = 1.01, 95%CI = 0.73-1.39; AG+AA vs. GG: OR = 0.91, 95% CI = 00.74-1.11; and AA vs. AG+GG: OR = 0.83, 95% CI = 00.57-1.21); the results of adjusted data also showed no significant relationship. Subgroup analyses based on ethnicity, participants' smoking status, HWE in controls and severity of CP all revealed similar results to that of the overall analysis. Sensitivity analysis indicated the results were robust and no evidence of publication bias was found. Conclusions: Our meta-analysis suggests that DEFB1 rs11362 polymorphism may not have an important effect on the risk of CP. Further large-scale and well-designed studies are necessary to validate our conclusion in the future.

Levels, congener profiles, and dietary intake assessment of polychlorinated dibenzo-p-dioxins/dibenzofurans and dioxin-like polychlorinated biphenyls in beef, freshwater fish, and pork marketed in Guangdong Province, China.

Persistent organic pollutants such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs) consisting of non-ortho and mono-ortho PCBs are suggested to be very hazardous and have adverse effects on human health. However, their levels and congener profiles in retail foods marketed in Guangdong Province of China have not been elucidated thus far. Thus, in this study, 226 individual samples of beef, freshwater fish, and pork marketed across four regions of Guangdong Province were randomly collected during 2013-2015 to determine their levels of PCDD/Fs and DL-PCBs. The results showed that the total toxic equivalency quantities (TEQs) of most samples were below the maximum limits except for the 26 samples collected from the vicinities of pollution areas. The median total TEQs of these three categories were 0.174, 0.488, and 0.113pgTEQ/g fw, respectively, which indicated that the contamination status of the studied foods was not serious. For congener profiles, significantly different patterns were observed in three food groups, but with the same major TEQ contributors being 2,3,4,7,8-PeCDF in beef, freshwater fish, and pork. Regional differences of congener profiles in each food group were also found in this study, which might be attributed to the regionally different distributions of PCDD/Fs and DL-PCBs in environment media. The dietary exposures of four population subgroups (girls, boys, male adults, and female adults) to PCDD/Fs and DL-PCBs via three food groups were estimated to assessed the potential risks. They were all lower than the provisional tolerable monthly intake (PTMI, 70pgTEQ/kgbw/month) established by Joint FAO/WHO Expert Committee on Food Additive. In these food categories, the exposure to PCDD/Fs and DL-PCBs via freshwater fish was the highest one, which accounted for about 20% of PTMI, indicating that it was the major route to expose dioxin compounds.

Raman spectrum: A potential biomarker for embryo assessment during in vitro fertilization.

The aim of the study was to investigate whether Raman spectrum is consistent with the morphological scoring of the embryo of day 3 during in vitro fertilization (IVF). The spent culture media of embryo of day 3 from 10 patients were collected and analyzed. The samples were analyzed using Raman spectroscopy and graded according to the standard embryo scoring system simultaneously. Data showed that the Raman spectra obtained from the droplet of media were useful, as they can act as the characteristic signature for protein and amino acids. The Raman biospectroscopy-based metabonomics profiling of spent media was consistent with the result of conventional morphological evaluation. In conclusion, this technology offers great potential for the development of tools allowing rapid non-invasive assessment of the quality of embryo of day 3 during IVF.

Reliability and validity of center of pressure measures for balance assessment in older adults.

[Purpose] This study was conducted to assess the reliability and validity of center of pressure-based parameters for balance assessment. [Subjects and Methods] Two hundred and forty older adults were evaluated using a force platform and the Berg Balance Scale at 1-week intervals. The intra-class correlation coefficient and the Pearson correlation coefficient were used to test reliability and validity respectively. [Results] The reliability of the 12 selected center of pressure measures was satisfactory (intra-class correlation coefficient = 0.75-0.99) and the validity between the parameters and the Berg Balance Scale was moderate to good (r = -0.62 to -0.88). [Conclusion] Center of pressure-based parameters are reliable and valid measures in older adults.

[Distribution, sources and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in surface sediments of Yangtze estuary and Zhejiang coastal areas].

PAHs contents of surface sediments were tested from 62 sampling sites of the Yangtze River estuary and Zhejiang coastal zone in 2013. The results showed that: 16 kinds of PAHs, which are listed as priority pollutants by EPA, were found in all the samples. The total PAHs level (dry weight) reached 31. 8-384 µg x kg(-1) and the average amount was 131.1 µg x kg(-1). The distribution of PAHs was affected by terrigenous input and point source pollution, the high-value zones were found at 2# sampling site of the Yangtze River estuary and 21# sampling site of Ningbo. Compared with other sea areas, the survey sea area was at a low PAHs pollution level. PAHs were primarily tetracyclic or tricyclic, and source analysis showed that most of PAHs were originated from combustion of wood and coal. Based on the Sediment Quality Guidelines (SQGs), the assessment result showed that the PAHs content of surface sediments from survey sea area was at a relatively low level of ecological risk; While according to the assessment result of the Sediment Quality Standards (SQSs), PAHs pollution of surface sediments from survey sea area displayed an "Obviously negative ecological effect" to some extent, and some countermeasures are required to control and eliminate pollutions.

A systematic review and quantitative assessment of sleep-disordered breathing during pregnancy and perinatal outcomes.

PURPOSE: Previous investigations have suggested a strong association between sleep-disordered breathing (SDB) during pregnancy and perinatal outcomes. However, the results of the following replication studies were not always concordant. Therefore, this meta-analysis was conducted to evaluate the more reliable estimate. METHODS: A systematic literature search was performed on PubMed, Springer Link, and EMBASE to identify all eligible studies published before August 2013. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed or random effects model. RESULTS: A total of 24 publications met the inclusion criteria and were included in this meta-analysis. Findings demonstrated that moderate-to-severe SDB during pregnancy was associated with gestational diabetes mellitus (OR=1.78; 95% CI, 1.29 to 2.46), pregnancy-related hypertension (OR=2.38; 95% CI, 1.63 to 3.47), preeclampsia (OR=2.19; 95% CI, 1.71 to 2.80), preterm delivery (OR=1.98; 95% CI, 1.59 to 2.48), low birth weight (OR=1.75; 95% CI, 1.33 to 2.32), neonatal intensive care unit (NICU) admission (OR=2.43; 95% CI, 1.61 to 3.68), intrauterine growth restriction (OR=1.44; 95% CI, 1.22 to 1.71), and Apgar score of <7 at 1 min (OR=1.78; 95% CI, 1.10 to 2.91) based on all studies but not gestational age and birth weight. CONCLUSIONS: This meta-analysis revealed that moderate-to-severe SDB during pregnancy may be associated with most of adverse perinatal outcomes. Further well-designed studies are warranted to confirm our findings.

Accuracy assessment on the analysis of unbound drug in plasma by comparing traditional centrifugal ultrafiltration with hollow fiber centrifugal ultrafiltration and application in pharmacokinetic study.

In present study, accuracy assessment on the analysis of unbound drug in plasma was made by comparing traditional centrifugal ultrafiltration (CF-UF) with hollow fiber centrifugal ultrafiltration (HFCF-UF). We used metformin (MET) as a model drug and studied the influence of centrifugal time, plasma condition and freeze-thaw circle times on the ultrafiltrate volume and related effect on the measurement of MET. Our results demonstrated that ultrafiltrate volume was a crucial factor which influenced measurement accuracy of unbound drug in plasma. For traditional CF-UF, the ultrafiltrate volume cannot be well-controlled due to a series of factors. Compared with traditional CF-UF, the ultrafiltrate volume by HFCF-UF can be easily controlled by the inner capacity of the U-shaped hollow fiber inserted into the sample under enough centrifugal force and centrifugal time, which contributes to a more accurate measurement. Moreover, the developed HFCF-UF method achieved a successful application in real plasma samples and exhibited several advantages including high precision, extremely low detection limit and perfect recovery. The HFCF-UF method offers the advantage of highly satisfactory performance in addition to being simple and fast in pretreatment, with these characteristics being consistent with the practicability requirements in current scientific research.

Subjective well-being of the elderly in Xi Cheng District, Beijing.

BACKGROUND: In 2010 the Beijing Municipal Government promulgated a policy aimed at improving the quality of life and subjective well-being of elderly residents that included a component focused on mental health. AIM: Identify factors associated with subjective well-being in a representative sample of elderly residents of Xi Cheng District in Beijing. METHODS: This cross-sectional study administered a self-completion survey to a stratified random sample of 2342 residents of Xi Cheng District who were 60 to 80 years of age. The level of well-being was assessed using a validated Chinese version of the Memorial University of Newfoundland Scale of Happiness (MUNSH). Detailed socioeconomic variables were obtained using a questionnaire developed by the authors. Social support, anxiety, and depression were assessed using validated Chinese versions of the Social Support Rating Scale (SSRS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: Among the 2342 respondents, 1616 (69.0%) had a total MUNSH score of 32 or above, indicating a high level of happiness; 423 (18.1%) has a total SSRS score 32 or below, indicating poor social support; 201 (8.6%) had a total SDS score of 53 or above, indicating significant depression; and 126 (5.3%) had a total SAS score of 50 or above, indicating significant anxiety. In the multivariate regression analysis the self-reported level of depression was the most important factor related to well-being. Anxiety, social support, income level, the quality of family relationships, the ability to self-regulate emotions, and regular exercise were also significantly related to well-being; but gender, marital status, age and educational level were not associated with well-being. CONCLUSION: Among elderly urban residents in Beijing, self-reports of poor subjective well-being are closely associated with self-reports of depressive and anxiety symptoms and also associated with social factors such as social support, income level and family relationships. Prospective studies are needed to identify the causal relationships of these variables and, based on the findings, to develop targeted interventions aimed at improving the quality of life and well-being of elderly community members.

[Factors associated with attitudes toward tobacco control policy in public places among adults in three counties of China].

OBJECTIVE: vestigate the attitudes of urban and rural community members toward total banning on smoking in public places and to explore the factors associated with these attitudes, in three counties/cities in China. METHODS: A cross-sectional study was conducted in three counties/cities in 2004, including Xin' an county of Henan province, Anyi county of Jiangxi province, and Mianzhu city of Sichuan province. A total of 5642 residents at age of 18-69 years old were interviewed face-to-face with a uniform questionnaire by locally-trained interviewers, through a random three-stage stratified sampling in each county. Factors were assumed to be associated with attitudes, using chi-square test in univariate analysis and non-conditional logistic regression model in multivariate analysis. RESULTS: The prevalence of current smoking among respondents was 44.3%. 80.7% (1379/1709) of the current smokers reported smoking often or sometimes in public places. Only 9.6% (479/4983) of the respondents reported that their indoor workplaces had totally banned on smoking. 43.5% of the respondents supported a total smoking ban strategy in pubic venues. The results of multivariate logistic regression model showed that eight factors were significantly associated with support for the total smoking ban in public places included region, residency, age, gender, education, smoking status, awareness about passive smoking hazards, and hearing of any message on tobacco control through media differences of rates regarding the factors as: residents in urban to rural areas (OR = 1.29), elderly to youngsters (30-49 vs. 18-29, OR = 1.46; 50-69 vs. 18-29, OR = 1.71), female to male (OR = 1.27), high-educated to less-educated ones, quitters to current smokers (OR = 1.90), nonsmokers to current smokers (OR = 2.01). Those who know messages on health hazards of passive smoking (OR = 2.26), or heard of message on tobacco control through media (OR = 1.43). CONCLUSION: Results from our study revealed that a thorough smoke-free policy in public places should be developed and implemented in these three counties/cities.

Exploring barriers to implementation of smoking policies: a qualitative study on health professionals from three county-level hospitals.

OBJECTIVE: This study was to identify factors limiting the implementation of smoking policies in county-level hospitals. METHODS: We conducted qualitative interviews (17 focus groups discussions and 6 one-to-one in depth interviews) involving 103 health professionals from three target county-level hospitals. A combination of purposive and convenience sampling was used to recruit subjects and gain a broad range of perspectives on issues emerging from ongoing data-analysis until data saturation occurred. The transcripts were analyzed for themes and key points. RESULTS: The main themes that emerged suggested that both smokers and non-smokers viewed smoking very negatively. However, it was clear that, underlying this acceptance of the health risks of smoking, there was a wide range of beliefs. Most of the health professionals pointed out that, as smoking was legal, addictive, and influenced by social norms, currently it was almost unrealistic to expect all smokers to give up smoking or not to smoke in the hospitals. Furthermore, they were concerned about the potentially detrimental effects of providing counseling advice to all smokers on the interpersonal relationship among colleagues or between doctors and patients. In addition, low level of employee participation influenced the sustainable implementation of smoking policies. CONCLUSIONS: Simply being aware of the health risks about smoking did not necessarily result in successful implementation of the smoking policies. Application of comprehensive intervention strategies such as implementing smoking policies in public places at the county level, creating supportive environments, promoting community participation, and conducting health education, may be more effective.

Group sequential t-test for clinical trials with small sample sizes across stages.

Interim analyses are often applied in clinical trials for various reasons. To assess the effect of a clinical treatment, the group sequential t-test with a fixed number of interim analyses is frequently used in clinical trials. The existing critical values used in group sequential t-tests are obtained from normal approximations of t-statistics. In practice, however, normal approximation is not accurate when some sample sizes of treatment arms in some stages are small. In this paper, instead of using normal approximation, we directly obtain the critical values via a Monte Carlo method. We list some critical values for certain sample sizes and number of interim analyses, and provide some SAS code for general situations. We also consider the sample size calculation and run some simulations to check the accuracy of our critical values. The simulation results show that our critical values yield type I error probabilities that are very close to the nominal significance level, whereas the existing critical values based on normal approximation are not accurate when some sample sizes are small across stages.

[Ecological service assessment of human-dominated freshwater ecosystem with a case study in Yangzhou Prefecture, China.

Freshwater ecosystems provide a host of services to humanity. These services are now rapidly being lost, not least because of the inability of making the impacts measurable. To overcome this obstacle, assessment frameworks for freshwater ecosystem services are needed. A simple water equivalent framework to assess the ecological services provided by freshwater ecosystems was developed in this study. It translated the occupation of freshwater ecosystem services into biologically freshwater volumes and then compares this consumption to the freshwater throughput, that is, the ecological capacity available in this region. In this way, we use the example of Yangzhou Prefecture, to account the main categories of human occupation of water ecosystem services. The result showed that there is a huge gap between the consumption and the supply of freshwater ecosystem services. This must encourage local government to make land-use and water management decisions both economically rational and environmentally sound.

A measurement error model with a Poisson distributed surrogate.

We study a linear model in which one of the covariates is measured with error. The surrogate for this covariate is the event count in unit time. We model the event count by a Poisson distribution, the rate of which is the unobserved true covariate. We show that ignoring the measurement error leads to inconsistent estimators of the regression coefficients and propose a set of unbiased estimating equations to correct the bias. The method is computationally simple and does not require using supplemental data as is often the case in other measurement error analyses. No distributional assumption is made for the unobserved covariate. The proposed method is illustrated with an example from the Wisconsin Sleep Cohort Study.

Tests for inter-subject and total variabilities under crossover designs.

In this paper, we consider statistical tests for inter-subject and total variabilities between treatments under crossover designs. Since estimators of variance components for inter-subject variability and total variability in crossover design are not independent, the usual F-test cannot be applied. Alternatively, we propose a test based on the concept of the extension of the modified large sample method to compare inter-subject variability and total variability between treatments under a 2 x 2 m replicated crossover design. An asymptotic power of the proposed test is derived. A sensitivity analysis is performed based on the asymptotic power to determine how the power changes with respect to various parameters such as inter-subject correlation and intra-class correlation. Also the two methods for sample size calculation for testing total variability under 2 x 4 crossover design are discussed. The method based on the Fisher-Cornish inversion shows better performance than the method based on the normal approximation. Several simulation studies were conducted to investigate the finite sample performance of the proposed test. Our simulation results show that the proposed test can control type I error satisfactorily.

On the assessment of similarity for dissolution profiles of two drug products.

The assessment of similarity between dissolution profiles of two drug products is considered. After reviewing some existing approaches, we propose a statistical method of assessing local and global similarities based on a time series model for the ratio of the dissolution results from two drug products and a polynominal model for the mean of the ratio. An example is presented for illustration.

Assessing sensitivity and similarity in bridging studies.

In pharmaceutical industry, the sponsors are interested in bringing their drug products from one region (e.g., the United States of America) to another region (e.g., Asian Pacific) to increase the exclusivity of the drug products in the marketplace. However, it is a concern whether the clinical results can be extrapolated from the target patient population in one region to a similar but different patient population in a new region due to a possible difference in ethnic factors. The International Conference on Harmonization (ICH) recommends that a bridging study may be necessarily conducted to extrapolate the clinical results between regions. However, little or no information regarding the criterion for determining whether a bridging study is necessary based on the evaluation of the complete clinical data package is provided by the ICH. Furthermore, no criterion on the assessment of similarity of clinical results between regions is given. In this paper, we propose the use of a sensitivity index as a possible criterion for regulatory authorities in the new region to evaluate whether a bridging clinical study should be conducted and the sample size of such a bridging clinical study. A criterion and a statistical method for assessment of similarity of clinical results between regions are also proposed, using the concept of population bioequivalence [FDA. Guidance for Industry--Statistical Approaches to Establishing Bioequivalence, Center for Drug Evaluation and Research, Food and Drug Administration: Rockville, MD, 2001] assuming that study site is random.

Testing model fit in longitudinal data analysis against alternatives with omitted covariates.

Several types of common model misspecifications can be re-formulated as problems of omitted covariates. These include situations with unmeasured confounders, measurement errors in observed covariates and informative censoring. Longitudinal data present special opportunities for detecting omitted covariates that are related to the observed ones differently across time than across individuals. This situation arises with period and cohort effects, as well as with usual formulations of classical measurement error in observed covariates. In this article we focus on testing for the existence of omitted covariates in longitudinal data analysis when models are fit by generalized estimation equations. When omitted covariates are present, specification of the correct link function conditionally on only observed covariates under the alternative usually involves complicated numerical integration. We propose a quasi-score test statistic that avoids the need to fit such alternative models. The statistic is asymptotically chi-square distributed under the null hypothesis of no omitted covariates with degrees of freedom determined by the assumed alternative structure. We study the significance level and the power of the quasi-score test in linear and logistic regression models. The test is then applied to an analysis of excessive daytime sleepiness.