[Potential Ecological Risk Characteristics and Source Apportionment of Heavy Metals in Farmland Soils around Typical Factories in Hunan Province Based on Monte-Carlo Simulation].

In order to explore the pollution characteristics， ecological risks， and pollution sources of heavy metals in farmland soils around typical factories in Hunan Province， the content characteristics of eight heavy metals in farmland soils around fluoride factories， leather factories， and plating plants were analyzed. The geo-accumulation index and potential ecological risk index were used to evaluate the pollution and environmental risk of heavy metals. The correlation analysis， hierarchical cluster analysis， and principal component analysis were used to analyze the sources of heavy metals. The Monte-Carlo model was used to evaluate the probability risk of regional ecological risk. The results showed that the main pollution elements in the soil were Cd and Zn， and their mean values were 4.46 and 2.73 times the background values， respectively. Zn was at a mild pollution level in the soil of the three typical factories， and Cd was at a moderate pollution level in the whole fluoride factory. The pollution sources of heavy metals in the typical factories were mainly natural sources， industrial activity sources （industrial waste discharge， mineral mining， and smelting activities）， traffic sources， etc. The results of potential ecological risk assessment showed that the ecological risk of the fluoride factory was at a high risk level， and the ecological risk of the leather factory and plating plants was at a high risk level. Cd was the main contributing element. The results of Monte-Carlo probabilistic ecological risk assessment reduced the uncertainty of deterministic assessment， which could provide scientific basis for accurate risk management and control in the regions.

A new comprehensive quantitative index for the assessment of essential amino acid quality in beef using Vis-NIR hyperspectral imaging combined with LSTM.

The quality of beef is usually predicted by measuring a single index rather than a comprehensive index. To precisely determine the essential amino acid (EAA) contents in 360 beef samples, the feasibility of optimized spectral detection techniques based on the comprehensive EAA index (CEI) and comprehensive weight index (CWI) constructed by factor analysis was explored. Two-dimensional correlation spectroscopy (2D-COS) was used to analyse the mechanisms of spectral peak shifts in complex disturbance systems with CEI and CWI contents, and 15 sensitive feature variables were extracted to establish a quantitative analysis model of a long short-term memory network (LSTM). The results indicated that 2D-COS had good predictive performance in both CEI-LSTM (R2P of 0.9095 and RPD of 2.76) and CWI-LSTM (R2P of 0.8449 and RPD of 2.45), which reduced data information by 88%. This indicates that utilizing 2D-COS can eliminate collinearity and redundant information among variables while achieving data dimensionality reduction and simplification of calibration models. Furthermore, a spatial distribution map of the comprehensive EAA content was generated by combining the optimal prediction model. This study demonstrated that the comprehensive index method furnishes a new approach to rapidly evaluate EAA content.

[Spatial and Temporal Distribution Characteristics of Heavy Metals in Main Rivers Sediments and Ecological Risk Assessment in Kaifeng City].

Heavy metal pollution in urban river sediments is an important threat to river ecosystem health. To explore the temporal and spatial distribution characteristics of heavy metals in river sediments of Kaifeng City, the surface sediments of rivers were sampled in 2015 and 2021, respectively, and the contents of Cd, Cr, Cu, Ni, Pb, and Zn in sediments at different periods were compared. The heavy metal pollution in the two periods was evaluated using the indices of geo-accumulation, bio-toxicity risk assessment, and potential ecological risk. The results showed that the content of heavy metals in river sediments of Kaifeng City in 2021 were decreased significantly compared with that in 2015. Cd, Cr, Cu, Ni, Pb, and Zn decreased by 94.42%, 18.4%, 85.7%, 45.19%, 75.61%, and 92.28%, respectively. The heavy metal content in the Huafei River and Huiji River was higher than that in other rivers in both periods. Correlation and principal component analyses showed that the heavy metal pollution sources of river sediments in Kaifeng City were highly similar, and human activities such as industrial layout, road traffic, and land use were the main pollution sources. However, the results showed that the main pollutants were different between the two sampling times. In 2015, Cd, Cr, Pb, and Zn were the main pollutants, and in 2021, Cd, Cu, Pb, and Zn were the main pollutants. The results of the geo-accumulation, bio-toxicity risk assessment, and potential ecological risk indices showed that the temporal and spatial differences in heavy metal pollution in river sediments in Kaifeng City were large. However, the heavy metal pollution of the Huiji River and Huafei River was still serious, with contents in the medium and high pollution levels, especially to Cd. The heavy metal treatment of rivers in Kaifeng City has a long way to go, and it is particularly necessary to strengthen the engineering treatment for key river sections and effectively monitor key pollution elements.

Combination of hyperspectral imaging and entropy weight method for the comprehensive assessment of antioxidant enzyme activity in Tan mutton.

The antioxidant enzymes play the crucial role in inhibiting mutton spoilage. In this study, visible near-infrared (Vis-NIR) hyperspectral imaging (HSI) combined with entropy weight method (EWM) was developed for the first time to evaluate the antioxidant properties of Tan mutton. The comprehensive index of antioxidant enzymes (AECI) consisting of peroxidase (49.34%), catalase (37.97%) and superoxidase (12.69%) was constructed by the EWM. Partial least squares regression, least squares support vector machine and artificial neural networks (ANN) were developed based on characteristic wavelengths extracted by successful projections algorithm, uninformative variable selection, iteratively retains informative variables (IRIV), regression coefficient and competitive adaptive reweighted sampling (CARS). The textural features (TF) were extracted by the gray level co-occurrence matrix and fused with the spectral data to establish models. Visualization of the changes in antioxidant enzyme activity was constructed from the optimal model. In addition, two-dimensional correlation spectra (2D-COS) with AECI as a perturbation variable was used to identify spectral features, revealing chemical bond changes order under the characteristic peaks at 612-799-473-708-559 nm. The results showed that the IRIV-CARS-TF-ANN model performed the best, with prediction set coefficient of determination (RP2) of 0.8813, which improved 2.12%, 1.11% and 2.77% over the RP2 of full band, IRIV and IRIV-CARS, respectively. It was suggested that fusion data of HSI may effectively predict the activity of antioxidant enzymes in Tan mutton.

Distribution, Characteristics, and Management of Older Patients With Valvular Heart Disease in China: China-DVD Study.

Background: The epidemiology and management of valvular heart disease (VHD) have changed with economic development and population aging in China in recent decades. Objectives: This study sought to understand the distribution, etiology, and presentation and assess the current practice and outcomes of older patients with VHD in China. Methods: The authors conducted the first nationwide survey of older patients with VHD between September and December 2016 from 69 hospitals in 28 provinces and municipalities throughout China. Hospitalized patients over 60 years of age with moderate-to-severe VHD, infective endocarditis, or previous valvular intervention were consecutively enrolled. Results: Of 8,929 patients (median age of 69 years, 47.5% female), 8227 (92.1%) had native VHD. Mitral regurgitation was the most prevalent single VHD (26.9% of native VHD), followed by tricuspid regurgitation (16.5%), aortic regurgitation (10.6%), aortic stenosis (5.1%), and mitral stenosis (3.1%). Degenerative (37.2%), functional (21.8%), and rheumatic (15.0%) etiologies were the 3 most common causes. Among symptomatic patients with severe VHD, 37.3% underwent valvular intervention. The intervention rates decreased significantly with age across all types of VHD (P trend < 0.01). Valvular surgery covered 93.7% of interventions. The overall 1-year survival rate was 74.4% (95% CI: 63.4%-85.4%). Conclusions: This study provides a unique national insight into the contemporary spectrum and management of older VHD patients in China. With the increase in the health care demand, more resources and efforts are required for early detection, effective intervention, and targeting innovation on advanced therapeutic techniques and devices to improve the outcomes.

A Comprehensive Functional Assessment of Carboxylesterase 1 Nonsynonymous Polymorphisms.

Carboxylesterase 1 (CES1) is the predominant human hepatic hydrolase responsible for the metabolism of many clinically important medications. CES1 expression and activity vary markedly among individuals; and genetic variation is a major contributing factor to CES1 interindividual variability. In this study, we comprehensively examined the functions of CES1 nonsynonymous single nucleotide polymorphisms (nsSNPs) and haplotypes using transfected cell lines and individual human liver tissues. The 20 candidate variants include CES1 nsSNPs with a minor allele frequency >0.5% in a given population or located in close proximity to the CES1 active site. Five nsSNPs, including L40Ter (rs151291296), G142E (rs121912777), G147C (rs146456965), Y170D (rs148947808), and R171C (rs201065375), were loss-of-function variants for metabolizing the CES1 substrates clopidogrel, enalapril, and sacubitril. In addition, A158V (rs202121317), R199H (rs2307243), E220G (rs200707504), and T290M (rs202001817) decreased CES1 activity to a lesser extent in a substrate-dependent manner. Several nsSNPs, includingL40Ter (rs151291296), G147C (rs146456965), Y170D (rs148947808), and R171C (rs201065375), significantly reduced CES1 protein and/or mRNA expression levels in the transfected cells. Functions of the common nonsynonymous haplotypes D203E-A269S and S75N-D203E-A269S were evaluated using cells stably expressing the haplotypes and a large set of the human liver. Neither CES1 expression nor activity was affected by the two haplotypes. In summary, this study revealed several functional nsSNPs with impaired activity on the metabolism of CES1 substrate drugs. Clinical investigations are warranted to determine whether these nsSNPs can serve as biomarkers for the prediction of therapeutic outcomes of drugs metabolized by CES1.

Clinical Evaluation and Magnetic Resonance Imaging Assessment of Intradiscal Methylene Blue Injection for the Treatment of Discogenic Low Back Pain.

BACKGROUND: Low back pain is a common worldwide health problem and has a significant socioeconomic impact on public health. Internal disc disruption has been considered as the most common cause of low back pain. Various therapies, including interbody fusion, disc replacement, injection therapies, and thermal annular procedures have been utilized for the treatment of discogenic low back pain. Recently, a new method of intradiscal methylene blue injection has been introduced to treat discogenic low back pain, but the clinical outcomes are controversial. OBJECTIVES: To investigate the clinical outcomes and magnetic resonance imaging changes of intradiscal methylene blue injection for the treatment of discogenic low back pain. STUDY DESIGN: Observational study. SETTING: An interventional low back pain management practice in a university hospital. METHODS: A total of 33 patients were selected to be treated with intradiscal methylene blue injection. The clinical outcomes were evaluated by numeric rating scale and Oswestry Disability Index at pretreatment, one month, 3, 6, and 12 months after treatment. The magnetic resonance imaging changes of involved intervertebral discs were assessed by apparent diffusion coefficient and T2 values at pretreatment, 3, 6, and 12 months after treatment. RESULTS: All of the patients got a follow-up period up to 12 months. The mean numeric rating scale scores at pretreatment, one month, 3, 6, and 12 months after treatment were 6.54, 2.98, 3.23, 3.66, and 4.72, respectively. There was a minimum of 2 points reduction at one month, 3, and 6 months after treatment, but less than 2 points reduction at 12 months. There was at least 50% improvement on the Oswestry Disability Index at one month, 3, and 6 months after treatment, but not at 12 months. The mean apparent diffusion coefficient and T2 value were significantly higher at 6 and12 months after treatment compared to pretreatment, but there was no significant difference between pretreatment and 3 months after treatment. LIMITATIONS: This is an observational study with a relatively small sample size and short-term follow-up. CONCLUSIONS: The intradiscal methylene blue injection might be an effective therapy for discogenic low back pain for the short-term and could improve disc degeneration condition to some extent.Key words: Low back pain, discogenic pain, internal disc disruption, provocation discography, methylene blue, intradiscal injection, disc degeneration, magnetic resonance, imaging.

Impact of Influenza on Outpatient Visits, Hospitalizations, and Deaths by Using a Time Series Poisson Generalized Additive Model.

BACKGROUND: The disease burden associated with influenza in developing tropical and subtropical countries is poorly understood owing to the lack of a comprehensive disease surveillance system and information-exchange mechanisms. The impact of influenza on outpatient visits, hospital admissions, and deaths has not been fully demonstrated to date in south China. METHODS: A time series Poisson generalized additive model was used to quantitatively assess influenza-like illness (ILI) and influenza disease burden by using influenza surveillance data in Zhuhai City from 2007 to 2009, combined with the outpatient, inpatient, and respiratory disease mortality data of the same period. RESULTS: The influenza activity in Zhuhai City demonstrated a typical subtropical seasonal pattern; however, each influenza virus subtype showed a specific transmission variation. The weekly ILI case number and virus isolation rate had a very close positive correlation (r = 0.774, P < 0.0001). The impact of ILI and influenza on weekly outpatient visits was statistically significant (P < 0.05). We determined that 10.7% of outpatient visits were associated with ILI and 1.88% were associated with influenza. ILI also had a significant influence on the hospitalization rates (P < 0.05), but mainly in populations <25 years of age. No statistically significant effect of influenza on hospital admissions was found (P > 0.05). The impact of ILI on chronic obstructive pulmonary disease (COPD) was most significant (P < 0.05), with 33.1% of COPD-related deaths being attributable to ILI. The impact of influenza on the mortality rate requires further evaluation. CONCLUSIONS: ILI is a feasible indicator of influenza activity. Both ILI and influenza have a large impact on outpatient visits. Although ILI affects the number of hospital admissions and deaths, we found no consistent influence of influenza, which requires further assessment.

ELISA-PLA: A novel hybrid platform for the rapid, highly sensitive and specific quantification of proteins and post-translational modifications.

Detection of low-abundance proteins and their post-translational modifications (PTMs) remains a great challenge. A conventional enzyme-linked immunosorbent assay (ELISA) is not sensitive enough to detect low-abundance PTMs and suffers from nonspecific detection. Herein, a rapid, highly sensitive and specific platform integrating ELISA with a proximity ligation assay (PLA), termed ELISA-PLA, was developed. Using ELISA-PLA, the specificity was improved by the simultaneous and proximate recognition of targets through multiple probes, and the sensitivity was significantly improved by rolling circle amplification (RCA). For GFP, the limit of detection (LOD) was decreased by two orders of magnitude compared to that of ELISA. Using site-specific phospho-antibody and pan-specific phospho-antibody, ELISA-PLA was successfully applied to quantify the phosphorylation dynamics of ERK1/2 and the overall tyrosine phosphorylation level of ERK1/2, respectively. ELISA-PLA was also used to quantify the O-GlcNAcylation of AKT, c-Fos, CREB and STAT3, which is faster and more sensitive than the conventional immunoprecipitation and western blotting (IP-WB) method. As a result, the sample consumption of ELISA-PLA was reduced 40-fold compared to IP-WB. Therefore, ELISA-PLA could be a promising platform for the rapid, sensitive and specific detection of proteins and PTMs.

Assessment of fibrotic tissue and microvascular architecture by in-line phase-contrast imaging in a mouse model of liver fibrosis.

PURPOSE: To explore the value of in-line phase-contrast imaging with computed tomography (ILPCI-CT) by synchrotron radiation (SR) for liver fibrosis. MATERIALS AND METHODS: Liver fibrosis models were set up in 13 BALB/c mice by peritoneal injections of thioacetamide and evaluated by ILPCI-CT. Histological staging was used to categorize liver fibrosis into normal, mild fibrosis and advanced fibrosis groups. Microvessel density (MVD), the ratio of total vessel length to volume (L/V), the ratio of total number of branching points to liver volume (P/V) and the distribution of vessel diameter were assessed. RESULTS: The CT images showed slightly high-density shadows around the portal tracts in the fibrosis group. Three-dimensional reconstruction can detect vascular and nodular changes on the surface of fibrotic livers. The MVDs between the three groups were significantly different (P = 0.024). L/V was significantly different between the three groups (P = 0.014). There was a positive correlation between MVD and P/V. CONCLUSION: Fibrous material can be detected by ILPCI-CT even in the early stage of fibrosis. MVD, L/V, P/V and the distribution of vessel diameter were consistent with fibrosis-related angiogenesis progress. Three-dimensional reconstruction is a promising method to visualize morphological changes of the fibrotic liver. KEY POINTS: • ILPCI-CT can detect fibrous material even in the early stage of liver fibrosis. • MVD, L/V, P/V, and the distribution of vascular diameter reflect pathological angiogenesis. • 3D reconstruction could be a promising approach for detecting liver fibrosis.

An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study.

Milk thistle (Silybum marianum) extracts, one of the most widely used dietary supplements, contain a mixture of six major flavonolignans (silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin) and other components. However, the pharmacokinetics of the free individual flavonolignans have been only partially investigated in humans. Furthermore, antioxidant effects of the extract, which may underlie the basis of many therapeutic effects, have not been thoroughly assessed. The present study evaluated the pharmacokinetics of the six major flavonolignans in healthy volunteers receiving single doses of either one (175 mg), two (350 mg), or three (525 mg) milk thistle capsule(s) on three separate study visits. Additionally, the steady-state pharmacokinetic parameters were determined after the subjects were administered one capsule three times daily for 28 consecutive days. Our results demonstrated that all six flavonolignans were rapidly absorbed and eliminated. In order of abundance, the exposure to free flavonolignans was greatest for silybin A followed by silybin B, isosilybin B, isosilybin A, silychristin, and silydianin. The systemic exposure to these compounds appeared linear and dose proportional. The disposition of flavonolignans was stereoselective, as evidenced by the apparent clearance of silybin B, which was significantly greater than silybin A, whereas the apparent clearance of isosilybin B was significantly lower than isosilybin A. The concentrations of urinary 8-epi-prostaglandin F2α, a commonly used biomarker of oxidative status in humans, were considerably decreased in study subjects after a 28-day exposure to the extract (1.3 ± 0.9 versus 0.8 ± 0.9 ng/mg creatinine) but failed to reach statistical significance (P = 0.076).

BATMAN--an R package for the automated quantification of metabolites from nuclear magnetic resonance spectra using a Bayesian model.

MOTIVATION: Nuclear Magnetic Resonance (NMR) spectra are widely used in metabolomics to obtain metabolite profiles in complex biological mixtures. Common methods used to assign and estimate concentrations of metabolites involve either an expert manual peak fitting or extra pre-processing steps, such as peak alignment and binning. Peak fitting is very time consuming and is subject to human error. Conversely, alignment and binning can introduce artefacts and limit immediate biological interpretation of models. RESULTS: We present the Bayesian automated metabolite analyser for NMR spectra (BATMAN), an R package that deconvolutes peaks from one-dimensional NMR spectra, automatically assigns them to specific metabolites from a target list and obtains concentration estimates. The Bayesian model incorporates information on characteristic peak patterns of metabolites and is able to account for shifts in the position of peaks commonly seen in NMR spectra of biological samples. It applies a Markov chain Monte Carlo algorithm to sample from a joint posterior distribution of the model parameters and obtains concentration estimates with reduced error compared with conventional numerical integration and comparable to manual deconvolution by experienced spectroscopists. AVAILABILITY AND IMPLEMENTATION: http://www1.imperial.ac.uk/medicine/people/t.ebbels/ CONTACT: t.ebbels@imperial.ac.uk.

[Research progresses of the completed pediatrics projects funded by National Natural Science Foundation of China from 2002 to 2006].

OBJECTIVE: To understand the projects completion and research progresses in pediatrics which were funded by the National Natural Science Foundation of China (NSFC), and evaluate the accomplishment objectively and justly. METHODS: The completion status of projects in pediatrics funded by department of clinical medicine II from 2002 to 2006 was analysed retrospectively, and important research achievement and outstanding development in some projects were reported. RESULTS: During the period between 2002 and 2006, 420 articles were published, and the average was 8.1 papers per project, which included 56 papers that were published in journals indexed by SCI (the average was 1.1 papers per project). The completion of general project was better than that of "the Young Researchers Fund" and small grant project. Ten post-doctors, 102 doctors and 109 masters were trained. Two projects were awarded with the first grade prize and another 2 with the second grade prize at the provincial and ministerial level, 4 items applied for patent and 1 was granted. These completed projects, which were mainly related to 7 of 12 subspecialties in the field of pediatrics, such as the respiratory disease, nephrology, neurology, cardiology, endocrinology, hematology, neonatology, are the major portion of the application projects and subsidized projects funded by NSFC, and achieved great research progresses. CONCLUSION: During the period between 2002 and 2006, the 52 completed projects in pediatrics showed difference in the distribution and quality of accomplishment among subspecialties and among types of supported projects; there are some gaps between pediatrics and some other clinical basic subspecialties II, this situation released the research status and problems in development of pediatrics in China. The general projects completion was good, and many projects obtained research achievements, which reflect the leading function of NSFC in pediatric research.

[Assessment of current hospital capacity in Beijing in responding to potential influenza pandemic: an application on Flu Surge model].

INTRODUCTION: Based on the estimate results of the capacity and preparedness of Beijing hospitals to respond to pandemic influenza, using flu surge model to evaluate its applicable hypothesis and to provide government with sentient strategy in planning pandemic influenza. Through collection of medical resources information, we calculated the possible impaction on hospitals by Flu Surge model and explored the applicable hypothesis in model operation through a questionnaire, direct observation and group discussion in 3 hospitals in Beijing. Based on flu surge model estimation during a 6-week epidemic from a pandemic virus with 35% attack rate, Beijing would have had an estimation of 5 383 000 influenza illnesses, 2 691 500 influenza outpatients, 76 450 influenza hospitalizations and 14 508 excess deaths. For a 6-week period with 35% attack rate, there would be a peak demand for 8% of beds, 210% of ICU beds, and 128% of ventilators estimated. Outpatients in different level hospital were quite disproportionated with 1742/ hospital/day, 650/hospital/day, and 139/hospital/day respectively. The sampled health workers had a mastery of 63.4% of the total knowledge and skills of diagnosing and treating of influenza, 73.5% of them washed their hands and 63.5% used PPE correctly. The total beds capacity, medical beds capacity and respiratory medical beds capacity would increase 8%, 35% and 128% respectively. CONCLUSION: The estimation results could be referenced when planning the pandemic strategy, but the results should be treated objectively when considering the hypothesis and practical situation in this model being used.