Quantitative structure-activity relationship model development for estimating the predicted No-effect concentration of petroleum hydrocarbon and derivatives in the ecological risk assessment.

Quantitative structure-activity relationship (QSAR) is a cost-effective solution to directly and accurately estimating the environmental safety thresholds (ESTs) of pollutants in the ecological risk assessment due to the lack of toxicity data. In this study, QSAR models were developed for estimating the Predicted No-Effect Concentrations (PNECs) of petroleum hydrocarbons and their derivatives (PHDs) under dietary exposure, based on the quantified molecular descriptors and the obtained PNECs of 51 PHDs with given acute or chronic toxicity concentrations. Three high-reliable QSAR models were respectively developed for PHDs, aromatic hydrocarbons and their derivatives (AHDs), and alkanes, alkenes and their derivatives (ALKDs), with excellent fitting performance evidenced by high correlation coefficient (0.89-0.95) and low root mean square error (0.13-0.2 mg/kg), and high stability and predictive performance reflected by high internal and external verification coefficient (Q2LOO, 0.66-0.89; Q2F1, 0.62-0.78; Q2F2, 0.60-0.73). The investigated quantitative relationships between molecular structure and PNECs indicated that 18 autocorrelation descriptors, 3 information index descriptors, 4 barysz matrix descriptors, 6 burden modified eigenvalues descriptors, and 1 BCUT descriptor were important molecular descriptors affecting the PNECs of PHDs. The obtained results supported that PNECs of PHDs can be accurately estimated by the influencing molecular descriptors and the quantitative relationship from the developed QSAR models, that provided a new feasible solution for ESTs derivation in the ecological risk assessment.

Evaluation of inpatient services of tertiary comprehensive hospitals based on DRG payment.

Objective: This study aims to evaluate inpatient services in 49 tertiary comprehensive hospitals using indicators from the diagnosis related groups (DRG) payment system. Method: DRG data from 49 tertiary comprehensive hospitals were obtained from the quality monitoring platform for provincial hospitals, and relevant indicators were identified. The analytic hierarchy process (AHP) was used to compute the weight of each indicator. The rank sum ratio method was used to calculate the weight rank sum ratio (WRSR) value and the corresponding probit value of each hospital. The hospitals were divided into four grades based on the threshold value: excellent, good, fair, and poor. Results: Eight indicators of the 49 hospitals were scored, and the hospital rankings of indicators varied. The No. 1 hospital ranked first in the indicators of "total number of DRG", "number of groups", and "proportion of relative weights (RW) ≥ 2". The WRSR value of the No.1 hospital was the largest (0.574), and the WRSR value of the No. 44 hospital was the smallest (0.139). The linear regression equation was established: WRSRpredicted =-0.141+0.088*Probit, and the regression model was well-fitted (F = 2066.672, p < 0.001). The cut-off values of the three WRSRspredicted by the four levels were 0.167, 0.299, and 0.431, respectively. The 49 hospitals were divided into four groups: excellent (4), good (21), average (21), and poor (3). There were significant differences in the average WRSR values of four categories of hospitals (p < 0.05). Conclusion: There were notable variances in the levels of inpatient services among 49 tertiary comprehensive hospitals, and hospitals of the same category also showed different service levels. The evaluation results contribute to the health administrative department and the hospital to optimize the allocation of resources, improve the DRG payment system, and enhance the quality and efficiency of inpatient services.

Peptide-based capture-and-release purification of extracellular vesicles and statistical algorithm enabled quality assessment.

Circulating extracellular vesicles (EVs) have gained significant attention for discovering tumor biomarkers. However, isolating EVs with well-defined homogeneous populations from complex biological samples is challenging. Different isolation methods have been found to derive different EV populations carrying different molecular contents, which confounds current investigations and hinders subsequent clinical translation. Therefore, standardizing and building a rigorous assessment of isolated EV quality associated with downstream molecular analysis is essential. To address this need, we introduce a statistical algorithm (ExoQuality Index, EQI) by integrating multiple EV characterizations (size, particle concentration, zeta potential, total protein, and RNA), enabling direct EV quality assessment and comparisons between different isolation methods. We also introduced a novel capture-release isolation approach using a pH-responsive peptide conjugated with NanoPom magnetic beads (ExCy) for simple, fast, and homogeneous EV isolation from various biological fluids. Bioinformatic analysis of next-generation sequencing (NGS) data of EV total RNAs from pancreatic cancer patient plasma samples using our novel EV isolation approach and quality index strategy illuminates how this approach improves the identification of tumor associated molecular markers. Results showed higher human mRNA coverage compared to existing isolation approaches in terms of both pancreatic cancer pathways and EV cellular component pathways using gProfiler pathway analysis. This study provides a valuable resource for researchers, establishing a workflow to prepare and analyze EV samples carefully and contributing to the advancement of reliable and rigorous EV quality assessment and clinical translation.

A Quantitative Structure-Activity Relationship Approach to Determine Biotoxicity of Amide Herbicides for Ecotoxicological Risk Assessment.

Amide herbicides have been widely applied in agriculture and found to be widespread and affect nontarget organisms in the environment. To better understand the biotoxicity mechanisms and determine the toxicity to the nontarget organisms for the hazard and risk assessment, five QSAR models were developed for the biotoxicity prediction of amide herbicides toward five aquatic and terrestrial organisms (including algae, daphnia, fish, earthworm and avian species), based on toxicity concentration and quantitative molecular descriptors. The results showed that the developed models complied with OECD principles for QSAR validation and presented excellent performances in predictive ability. In combination, the investigated QSAR relationship led to the toxicity mechanisms that eleven electrical descriptors (EHOMO, ELUMO, αxx, αyy, αzz, µ, qN-, Qxx, Qyy, qH+, and q-), four thermodynamic descriptors (Cv, Sθ, Hθ, and ZPVE), and one steric descriptor (Vm) were strongly associated with the biotoxicity of amide herbicides. Electrical descriptors showed the greatest impacts on the toxicity of amide herbicides, followed by thermodynamic and steric descriptors.

Impact of DRGs-based inpatient service management on the performance of regional inpatient services in Shanghai, China: an interrupted time series study, 2013-2019.

BACKGROUND: The asymmetry of information brings difficulty for government to manage public hospitals. Therefore, Jiading District of Shanghai has been establishing DRGs-based inpatient service management system (ISMS) to effectively compare the output of different hospitals through DRGs, reward desired hospital performance and enhance inpatient service capacity. However, the impact of the implementation of DRGs-based inpatient service management (ISM) policy in Jiading district is still unknow. We therefore conducted this study to evaluate the impact of DRGs-based ISM policy on the performance of inpatient service since its implementation in Jiading District, Shanghai, China in 2017. METHODS: Using an interrupted time series design, we analyzed quarterly data of seven DRGs-based performance measures from the ISMS which covered all five public hospitals in Jiading District from 2013 to 2019. We utilized the segmented linear regression model to assess the change of level and trend of performance indicators before and after ISM policy. Dickey-Fuller test was used to examine the stationary of the data. Durbin-Watson test was performed to check the series autocorrelation of indicators. RESULTS: Significant changes in the following indicators were observed since the implementation of ISM policy. The case-mix index (CMI) level decreased by 0.103 (P < 0.05), the trend increased by 0.008 (P < 0.05). The total weight level decreased by 3719.05 (P < 0.05), and the trend increased by 250.13 (P < 0.05). The time efficiency index (TEI) level increased by 0.12 (P < 0.05), and the trend decreased by 0.01 (P < 0.05). The cost efficiency index (CEI) level increased by 0.31 (P < 0.05), and the trend decreased by 0.02 (P < 0.05). No significant difference was found in the change of DRGs number, inpatient mortality of low-risk group cases (IMLRG) and inpatient mortality of medium-to-low risk group cases (IMMLRG). CONCLUSIONS: Findings highlight the role of ISM policy in improving the capacity and efficiency of regional inpatient service. Three prerequisites, including a good information system, high-quality EMR data, and a management team, are needed for other countries to implement their own ISM policy to help government manage public hospitals and improve the performance of regional inpatient service.

No expenditure difference among patients with liver cancer at stage I-IV: Findings from a multicenter cross-sectional study in China.

OBJECTIVE: The number of liver cancer patients in China accounts for more than half of the world. However, China currently lacks national, multicenter economic burden data, and meanwhile, measuring the differences among different subgroups will be informative to formulate corresponding policies in liver cancer control. Thus, the aim of the study was to measure the economic burden of liver cancer by various subgroups. METHODS: A hospital-based, multicenter and cross-sectional survey was conducted during 2012-2014, covering 39 hospitals and 21 project sites in 13 provinces across China. The questionnaire covers clinical information, sociology, expenditure, and related variables. All expenditure data were reported in Chinese Yuan (CNY) using 2014 values. RESULTS: A total of 2,223 liver cancer patients were enrolled, of whom 59.61% were late-stage cases (III-IV), and 53.8% were hepatocellular carcinoma. The average total expenditure per liver cancer patient was estimated as 53,220 CNY, including 48,612 CNY of medical expenditures (91.3%) and 4,608 CNY of non-medical expenditures (8.7%). The average total expenditures in stage I, II, III and stage IV were 52,817 CNY, 50,877 CNY, 50,678 CNY and 54,089 CNY (P>0.05), respectively. Non-medical expenditures including additional meals, additional nutrition care, transportation, accommodation and hired informal nursing were 1,453 CNY, 839 CNY, 946 CNY, 679 CNY and 200 CNY, respectively. The one-year out-of-pocket expenditure of a newly diagnosed patient was 24,953 CNY, and 77.2% of the patients suffered an unmanageable financial burden. Multivariate analysis showed that overall expenditure differed in almost all subgroups (P<0.05), except for sex, clinical stage, and pathologic type. CONCLUSIONS: There was no difference in treatment expenditure for liver cancer patients at different clinical stages, which suggests that maintaining efforts on treatment efficacy improvement is important but not enough. To furtherly reduce the overall economic burden from liver cancer, more effort should be given to primary and secondary prevention strategies.

Ecological risk assessment at the food web scale: A case study of a mercury contaminated oilfield.

Mercury, particularly methylmercury, can accumulate through food webs and generate high risks for species at higher trophic levels. Inorganic mercury can be methylated into the organic species methylmercury if suitable reducing conditions exist, for example, in hotspots like oilfields. We developed a conceptual model to conduct an ecological risk assessment based on the food web structure of the Shengli oilfield area, China. The model can identify species at risk and elucidate the sources of risks according to their diet. A risk rating criteria was developed based on the food web structure to categorize the different levels of risks for different species. As expected, the results indicate increasing risks for the biota higher in the food web hierarchy. Grasshoppers were mostly at no risk throughout the study area, whereas grubs at southwest were at minimal risks due to local high Hg concentration in the soil. Mantises, which are insect predators, were also at minimal risk. Herbivorous birds with similar feeding habits than grasshoppers were at no risk, but omnivorous and carnivorous birds were at moderate risk. The conceptual model is a useful tool to improve pollution remediation and establish risk control strategies based on ecological risks of the food web rather than just Hg concentrations in the environment.

Effect of Physical Activity on Hospital Service Use and Expenditures of Patients with Coronary Heart Disease: Results from Dongfeng-Tongji Cohort Study in China.

The intervention of behaviors, including physical activity (PA), has become a strategy for many hospitals dealing with patients with chronic diseases. Given the limited evidence available about PA and healthcare use with chronic diseases, this study explored the association between different levels of PA and annual hospital service use and expenditure for inpatients with coronary heart disease (CHD) in China. We analyzed PA information from the first follow-up survey (2013) of the Dongfeng-Tongji cohort study of 1460 CHD inpatients. We examined factors such as PA exercise volume and years of PA and their associations with the number of inpatient visits, number of hospital days, and inpatient costs and total medical costs. We found that the number of hospital days and the number of inpatient visits were negatively associated with intensity of PA level. Similarly, total inpatient and outpatient costs declined when the PA exercise volume levels increased. Furthermore, there were also significant associations between the number of hospital days, inpatient costs or total medical costs and levels of PA years. This study provides the first empirical evidence about the effects of the intensity and years of PA on hospital service use and expenditure of CHD in China. It suggests that the patients' PA, especially the vigorous PA, should be promoted widely to the public and patients in order to relieve the financial burden of CHD.

The Effects of Molecular Properties on Ready Biodegradation of Aromatic Compounds in the OECD 301B CO2 Evolution Test.

Ready biodegradation is the primary biodegradability of a compound, which is used for discriminating whether a compound could be rapidly and readily biodegraded in the natural ecosystems in a short period and has been applied extensively in the environmental risk assessment of many chemicals. In this study, the effects of 24 molecular properties (including 2 physicochemical parameters, 10 geometrical parameters, 6 topological parameters, and 6 electronic parameters) on the ready biodegradation of 24 kinds of synthetic aromatic compounds were investigated using the OECD 301B CO2 Evolution test. The relationship between molecular properties and ready biodegradation of these aromatic compounds varied with molecular properties. A significant inverse correlation was found for the topological parameter TD, five geometrical parameters (Rad, CAA, CMA, CSEV, and N c), and the physicochemical parameter K ow, and a positive correlation for two topological parameters TC and TVC, whereas no significant correlation was observed for any of the electronic parameters. Based on the correlations between molecular properties and ready biodegradation of these aromatic compounds, the importance of molecular properties was demonstrated as follows: geometrical properties > topological properties > physicochemical properties > electronic properties. Our study first demonstrated the effects of molecular properties on ready biodegradation by a number of experiment data under the same experimental conditions, which should be taken into account to better guide the ready biodegradation tests and understand the mechanisms of the ready biodegradation of aromatic compounds.

Bioaccessibility and Health Risk Assessment of Cu, Cd, and Zn in "Colored" Oysters.

Bioaccessibility describes the fraction of contaminants released from the food matrix into the digestive tracts of humans, which is beneficial for improving the health risk assessment of contaminants. In this study, the bioaccessibilities of cadmium (Cd), copper (Cu), and zinc (Zn) in two severely contaminated green oyster (Crassostrea angulate) and blue oyster (Crassostrea hongkongensis) populations were investigated. A human health risk assessment of these metals was then performed based on bioaccessibility measurements. Among the three metals, the bioaccessibility was the highest for Cu (42-95%), and Cd and Zn had comparable bioaccessibility (13-58%). There was no major difference in the bioaccessibility between green and blue oysters. A significant correlation between the tissue Cu and Zn concentrations was found in these highly contaminated oysters. A health risk assessment showed that all three metals in both oyster species seriously exceeded the levels recommended by the United States Environmental Protection Agency. Thus, oysters from these locations, and the metals contained therein, presented quite high risks for human consumption, which should be a great cause of concern. A significant relationship was only found between metal bioaccessibility and its tissue concentration instead of between metal bioaccessibility and subcellular distribution. In addition, a significant relationship was only observed between metal health risks and its tissue concentration. The influence of metal bioaccessibilities on the health risks was limited. This may suggest that in the case of the colored oysters examined in this study, metal concentration instead of metal subcellular distribution could be the driving factor of the metal bioaccessibility, and metal concentration, instead of metal bioaccessibility, could be the driving factor of the metal health risks.

Assessment of functional tag single nucleotide polymorphisms within the DRD2 gene as risk factors for post-traumatic stress disorder in the Han Chinese population.

BACKGROUND: Gene variations related to the dopaminergic pathway have been implicated in a number of neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). Dopamine D2 receptor (DRD2) has been shown to significantly contribute to neuropsychiatric disorders and may specifically contribute to predisposition to PTSD. This study aimed to evaluate the association of polymorphisms within the entire DRD2 gene with PTSD in a case-control study. MATERIALS AND METHODS: A total of 834 unrelated Han Chinese adults, including 497 healthy volunteers and 337 patients with PTSD, were used in this study. Fifteen tag single-nucleotide polymorphisms (tSNPs) were selected spanning the entire DRD2 gene through the construction of haplotype bins. Genotypes were gathered using an improved multiplex ligation detection reaction (iMLDR) technique. Allelic frequencies and clinical characteristics were compared in two independent Han Chinese populations. Moreover, the functionality of the rs2075652 and rs7131056 polymorphisms were assessed by measuring transcriptional enhancer activities. RESULTS: Fifteen tag SNPs were identified in the Han Chinese population and all were common SNPs. Among 15 tSNPs, two of them (rs2075652 and rs7131056) significantly associated with PTSD. PTSD individuals were more likely to carry the rs2075652A and rs7131056A allele compared to the controls (P<0.05). The haplotype GTGATCGCGCAGGCG, had a risk effect on PTSD occurrence (OR=1.75, 95% CI: 1.24-2.48, P=0.002). Additionally, the rs2075652 polymorphism contained intronic enhancer activities. CONCLUSIONS: The rs2075652 and rs7131056 polymorphisms, and the haplotype GTGATCGCGCAGGCG within the DRD2 gene, may be potential markers to predict susceptibility to PTSD.

Performance comparison of SNP detection tools with illumina exome sequencing data--an assessment using both family pedigree information and sample-matched SNP array data.

To apply exome-seq-derived variants in the clinical setting, there is an urgent need to identify the best variant caller(s) from a large collection of available options. We have used an Illumina exome-seq dataset as a benchmark, with two validation scenarios--family pedigree information and SNP array data for the same samples, permitting global high-throughput cross-validation, to evaluate the quality of SNP calls derived from several popular variant discovery tools from both the open-source and commercial communities using a set of designated quality metrics. To the best of our knowledge, this is the first large-scale performance comparison of exome-seq variant discovery tools using high-throughput validation with both Mendelian inheritance checking and SNP array data, which allows us to gain insights into the accuracy of SNP calling through such high-throughput validation in an unprecedented way, whereas the previously reported comparison studies have only assessed concordance of these tools without directly assessing the quality of the derived SNPs. More importantly, the main purpose of our study was to establish a reusable procedure that applies high-throughput validation to compare the quality of SNP discovery tools with a focus on exome-seq, which can be used to compare any forthcoming tool(s) of interest.

Toxicological effects involved in risk assessment of rare earth lanthanum on roots of Vicia faba L. seedlings.

Combined chemical analyses and biological measurements were utilized to investigate potential toxicological effects and possible mechanisms involved in risk assessment of rare earth elements (REEs) on Vicia faba L. seedlings, which were hydroponically cultivated and exposed to various concentrations of lanthanum (La) for 15 days. The results showed that La contents in both the solution and roots increased with the increase of extraneous La, contributing to hormetic dose responses of superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (GPX), ascorbate peroxidase (APX) and endoprotease (EP) isozymes activities, and HSP 70 production enhanced at low doses but suppressed at higher doses of La. These physiological responses constituted antioxidant and detoxification systems against La-induced oxidative stress. The elevated La levels also contributed to oxidatively modified proteins, which were most responsible for subsequent cell death and growth retardation of the roots. By combination of hormetic and traditional threshold dose levels, the threshold dose range was deduced to be 108-195 microg La/g dry weight in the roots, corresponding to 0.90-3.12 mg/L of soluble La in the culture solution. It suggests that persistent applications of REEs may lead to potential ecological risk in the environment.

Polyacrylamide gel photopatterning enables automated protein immunoblotting in a two-dimensional microdevice.

We demonstrate a two-dimensional microfluidic architecture that integrates polyacrylamide gel electrophoresis (PAGE) with immunoblotting in a fully automated format. This assay is designed to overcome performance limitations of conventional slab-gel immunoblotting, including multiple manual interventions, low-throughput transfer and blotting, and substantial consumption of reagents and sample. To unify PAGE with blotting in one device, this microfluidic approach makes use of high-resolution regional photopatterning of multiple polyacrylamide gel elements, and automated electrophoretic transport. A complete native immunoblot of free prostate specific antigen from human seminal fluid is demonstrated in less than 5 min. Further, the characterization of post-PAGE electrophoretic transfer showed high efficiency and minimal sample dispersion.