Assessment on malvidin-3-glucoside interaction with TLR4 via multi-spectroscopic analysis and molecular docking.

As one innate immune pattern recognition receptor, Toll-like receptor 4 (TLR4) recently has been considered as a critical player in glucolipid metabolism. Blueberries contain high level of anthocyanins, especially malvidin-3-glucoside (Mv-3-glc), which contribute the anti-inflammatory, hypoglycemic, and hypolipidemic effects. It is speculated that Mv-3-glc is able to possess these functions by binding to TLR4. Here, the noncovalent interactions of Mv-3-glc and TLR4 was explored through multi-techniques including fluorescence and ultraviolet-visible (UV-Vis) absorption spectroscopy, as well as molecular docking. The results demonstrated that Mv-3-glc was able to quench TLR4 intrinsic fluorescence effectively. A stable complex was formed spontaneously and the reaction was exothermic. The degree of binding of Mv-3-glc to TLR4 showed a strong dependence on the chemical concentration, temperature, and pH values. The negative signs for enthalpy (ΔH = -69.1 ± 10.8 kJ/mol) and entropy (ΔS = -105.0 ± 12.3 J/mol/K) from the interaction of the Mv-3-glc and TLR4 shows that the major driving forces are the hydrogen bonding and van der Waals' force, which is consistent with the molecular docking results. In addition, molecular docking predicted that the active center with specific amino acid residues, Phe126, Ser127, Leu54, Ile153, and Tyr131 was responsible for the site of Mv-3-glc binding to TLR4/myeloid differentiation protein-2 (MD-2). These findings confirmed that Mv-3-glc could bind to TLR4, which would be beneficial to understand the target therapeutic effects of blueberry anthocyanins on TLR4 in regulating glucolipid metabolism.

In vitro osteoclastogenesis assessment using murine myeloid-derived suppressor cells.

The study of myeloid-derived suppressor cells (MDSCs) has been commonly reported in the context of cancer immunology. MDSCs play a key role in cancer growth and progression by inhibiting both innate and adaptive immunity. In addition to the immunosuppressive function of MDSCs in cancer, a novel function of MDSCs as osteoclast precursors has recently been attracting attention. Because monocytic-MDSCs (M-MDSCs) are derived from the same myeloid lineage as macrophages, which are osteoclast progenitors, M-MDSCs can undergo differentiation into osteoclasts, contributing to bone destruction not only in the cancer microenvironment but also in inflammatory conditions including obesity and osteoarthritis. Herein, we present details of the technique to evaluate osteoclasts in vitro, as well as specific techniques to isolate M-MDSCs and identify them. This protocol can be easily adapted to isolate M-MDSCs from most pathologic conditions for easy evaluation.

Accounting for the cost of ecological degradation in Fuzhou City, China.

Ecological degradation accounting is a critical content of building green GDP and gross economic-ecological product (GEEP) accounting systems. With ecosystems in Fuzhou City as a research object, we built an accounting framework for the cost of ecological degradation according to the unreasonable human activity. Following the accounting framework, we calculated the ecological degradation cost in Fuzhou City of 2015 and 2018. The results showed that the ecological degradation cost in Fuzhou City of 2015 was 9.08 billion yuan, accounting for 1.6% of local GDP. For different ecosystem types, marine ecological degradation cost was the largest, about 6.311 billion yuan, accounting for 69.5% of the total loss, followed by wetland ecosystem, accounting for 28.7%, and then arable land, contributing only 1.8%. In term of functions, the cost of provisioning degradation was the largest, about 6.313 billion yuan, accounting for 69.5% of the total loss, followed by regulation loss, accounting for 27.5%, mainly from the loss of climate regulation and hydrological regulation. In the regional distribution, the ecological degradation cost was mainly concentrated in Lianjiang County, Luoyuan County, Fuqing City, and Minqing County, up to 8.092 billion yuan in total, accounting for 89.7% of total loss. Compared with 2015, the ecological degradation cost in 2018 decreased by 2.608 billion yuan, showing an obvious downward trend, with a decrease rate of 28.7%. The reductions were major in Lianjiang County (86.4%), Luoyuan County (14.8%), Fuqing City (19.9%), and Minqing County (12.6%), and mainly concentrated in marine and wetland ecosystems. Such a result indicated that people's awareness of ecological protection in Fuzhou City was increasing, and that the ecological damage due to human activity in marine and wetland system was obviously decreased. This study provided data support for promoting regional sustainable development and ecological civilization construction.

Temporal trends in incidence and mortality rates of laryngeal cancer at the global, regional and national levels, 1990-2017.

OBJECTIVES: Laryngeal cancer is the most prevalent entity of head and neck cancer. Knowing the trends of incidence and mortality of laryngeal cancer is important for the reduction in related disease burden. DESIGN: Population-based observational study. MAIN OUTCOMES AND MEASURES: The incidence and mortality data of laryngeal cancer were retrieved from the Global Burden of Disease study 2017 online database. The estimated average percentage change was used to quantify the trends of laryngeal cancer incidence and mortality at the global, regional and national levels. RESULTS: Globally, the numbers of incident cases and deaths due to laryngeal cancer increased 58.7% and 33.9%, respectively, from 1990 to 2017. However, the overall age-standardised incidence rate (ASIR) and age-standardised mortality rate decreased by 0.99% (95% CI 0.83% to 1.14%) and 1.62% (95% CI 1.50% to 1.74%) per year, respectively. These decreases were ubiquitous worldwide. However, unfavourable trends in the ASIR of laryngeal cancer were also observed in a total of 51 developing countries. CONCLUSIONS: The incidence and mortality rates of laryngeal cancer have significantly decreased at the global level and in most countries over the past three decades. The regions that showed an increasing incidence trend deserve more attention.

Genetic Diversity Assessment of a Chinese Medicinal Endemic Species, Aspidopterys obcordata var. obcordata, by Combined Molecular Marker Methods (ISSR & SRAP).

Aspidopterys obcordata var. obcordata, a medicinal plant endemic to China, is a narrowly distributed species and wild resources are extremely limited. To evaluate the genetic variability and degree of genetic divergence of A. obcordata var. obcordata, and to make rational scientific decisions on its harvest and germplasm conservation, we collected 122 samples from across nearly all of its distribution area and studied genetic diversity using inter-simple sequence repeats (ISSRs), sequence-related amplified polymorphisms (SRAPs), and a method combining the two techniques. The results revealed the high genetic diversity of A. obcordata var. obcordata, mainly due to its intra-population diversity, and the top two populations with the highest levels of intra-population diversity were ML and DH, individuals of which can serve as excellent germplasm candidates during the processing of germplasm screening and conservation. In general, the combining method was prior to the ISSR analyses and SRAP analyses results, except for a slight difference in the genetic structure of individual populations. Therefore, we suggest that a combination analysis of the two marker methods is ideal for evaluating the genetic diversity and genetic relationships of A. obcordata var. obcordata.

Spatial assessment models to evaluate human health risk associated to soil potentially toxic elements.

Quantifying source apportionment of potentially toxic elements (PTEs) in soils and associated human health risk (HHR) is essential for soil environment regulation and pollution risk mitigation. For this purpose, an integrated method was proposed, and applied to a dataset consisting of As, Cd, Cr, Cu, Hg, Ni, Pb, Se, and Zn in 273 soil surface samples. Positive matrix factorization (PMF) was used to quantitatively examine sources contributions of PTEs in soils; and the HHR arising from the identified source was determined by combining source profiles and health risk assessment; at last, sequential Gaussian simulation (SGS) was used to identify the areas with high HHR. Four sources were identified by PMF. Natural and agricultural sources affected all 9 PTEs contents with contributions ranging from 19.2% to 62.9%. 41.9% of Cd, 40.8% of Pb, 58.6% of Se, and 29.8% of Zn were controlled by industrial and traffic emissions. Metals smelting and mining explained 35.5%, 30.5%, and 24.9% of Cr, Cu, and Ni variations, respectively. Hg was dominated by atmospheric deposition from coal combustion and coking (58.7%). The mean values of the total non-carcinogenic risks of PTEs were 1.55 × 10-1 and 9.40 × 10-1 for adults and children, and the total carcinogenic risk of PTEs had an average value of 8.86 × 10-5. Based on source-oriented HHR calculation, natural and agricultural sources were the most important factor influencing HHR, explaining 51.0% and 49.1% of non-carcinogenic risks for children and adults, and 44.2% of carcinogenic risk. SGS indicated that 1.1% of the total area was identified as hazardous areas with non-carcinogens risk for children.

Clinical Utility and Cost Savings in Predicting Inadequate Response to Anti-TNF Therapies in Rheumatoid Arthritis.

INTRODUCTION: The PrismRA® test identifies rheumatoid arthritis (RA) patients who are unlikely to respond to anti-tumor necrosis factor (anti-TNF) therapies. This study evaluated the clinical and financial outcomes of incorporating PrismRA into routine clinical care of RA patients. METHODS: A decision-analytic model was created to evaluate clinical and economic outcomes in the 12-month period following first biologic treatment. Two treatment strategies were compared: (1) observed clinical decision-making based on a 175-patient cohort receiving an anti-TNF therapy as their first biologic after failure of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and (2) modeled clinical decision-making of the same population using PrismRA results to inform first-line biologic treatment choice. Modeled costs include biologic drug pharmacy, non-biologic pharmacy, and total medical costs. The odds of inadequate response to anti-TNF therapies and various components of patient care were calculated based on PrismRA results. RESULTS: Identifying predicted inadequate responders to anti-TNF therapies resulted in a modeled 38% increase in ACR50 response to first-line biologic therapies. The fraction of patients who achieved an ACR50 response to any therapy (TNFi and others) within the 12-month period was 33% higher in the PrismRA-stratified population than in the unstratified population (59 vs. 44%, respectively). When therapy prescriptions were modeled according to PrismRA results, cost savings were modeled for all financial variables: overall costs (4% decreased total, 19% decreased on ineffective treatments), total biologic drug pharmacy (4% total, 23% ineffective), non-biologic pharmacy (2% total, 19% ineffective), and medical costs (6% total, 19% ineffective). Female sex was the clinical metric that showed the greatest association with inadequate response to anti-TNF therapies (odds ratio 2.42, 95% confidence interval 1.20, 4.88). CONCLUSIONS: If PrismRA is implemented into routine clinical care as modeled, predicting which RA patients will have an inadequate response to anti-TNF therapies could save > $7 million in overall ineffective healthcare costs per 1000 patients tested and increase targeted DMARD response rates in RA.

Differential item functioning of the SF-12 in a population-based regional joint replacement registry.

BACKGROUND: Joint replacement, an increasingly common procedure amongst older adults, can substantially improve health-related quality of life (HRQoL). However, differential item functioning (DIF) may affect the accurate interpretation of differences in HRQoL amongst patients with different demographic and health status characteristics but the same underlying (i.e., latent) level of the investigated construct. This study tested for DIF in pre-operative SF-12 physical health (PH) and mental health (MH) sub-scale items amongst patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: Data were from a population-based joint replacement registry from the Canadian province of Manitoba. TKA and THA patients who had surgery between 2009 and 2015 and completed a pre-operative assessment were included. DIF was tested using the multiple indicators multiple causes (MIMIC) method with sex, age group, body weight status, and presence of multiple comorbid conditions (i.e., multimorbidity) as covariates. Analyses were stratified by joint type. RESULTS: The study cohort included 8820 patients; 42.1% underwent THA, 57.3% were female, 32.7% were 70+ years, and 52.8% were obese. For each sub-scale, four of the six items exhibited DIF in both THA and TKA groups. Differences in the covariate effect estimates for DIF and No-DIF models on the MH latent variable were largest for age and body weight status for the THA group, and for sex and multimorbidity for the TKA group. All of the differences were small for PH. Multimorbidity had the strongest association with PH and age and sex had the strongest association with MH in the DIF models. CONCLUSIONS: Demographic and health status characteristics influenced SF-12 PH and MH item responses in joint replacement populations, although the size of the effects were not large for PH. We recommend testing and adjusting for DIF effects to ensure comparability of HRQoL measures in joint replacement populations.

Cross-cultural validation of the educational needs assessment tool into Chinese for use in severe knee osteoarthritis.

BACKGROUND: Patient education is an integral part of the management of osteoarthritis. The educational needs assessment tool (ENAT) was developed in the UK to help direct needs-based patient education in rheumatic diseases. AIM: The aim of the study was to adapt and validate the ENAT into Chinese, for use in severe knee osteoarthritis (KOA). METHODS: This cross-cultural validation study took two phases: 1) adaptation of the ENAT into Chinese (CENAT) and 2) validation of the CENAT. The Construct validity was determined using factor analysis and criterion-related validity by comparing data from CENAT with data from different self-efficacy scales: patient-physician interactions scale (PEPPI-10), self-efficacy for rehabilitation outcome scale (SER), and the self-efficacy for exercise scale (SEE). RESULTS: The sample comprised 196 patients, with mean age 63.6±8.7 years, disease duration was11.5 years, and 57.1% were female. The CENAT was found to have high internal consistency. The CENAT had weak correlations with the Chinese versions of PEPPI r=0.40, SER r=0.40, and SEE r=0.39. There were no correlations with age r=-0.03 or disease duration r=-0.11. CONCLUSION: The ENAT translated well into Chinese and has evidence of validity in KOA. Future studies will further inform its usefulness in clinics, community, and online settings.

Preliminary study of the application of transthoracic echocardiography-guided three-dimensional printing for the assessment of structural heart disease.

OBJECTIVE: To investigate the feasibility and diagnostic value of a preoperative transthoracic echocardiography-guided three-dimensional printed model (TTE-guided 3DPM) for the assessment of structural heart disease (SHD). METHODS: Fourty-four patients underwent cardiac surgery at Tianjin Chest Hospital. The patients were preoperatively assessed using TTE-guided 3DPM, which was compared to conventional three-dimensional transthoracic echocardiography (3DTTE) along with direct intraoperative findings, which were considered the "gold standard." Twelve patients had SHD, including four with mitral prolapse, two with partial endocardial cushion defects, two with secondary atrial septal defects, two with rheumatic mitral stenosis, one with tetralogy of Fallot, and one with a ventricular septal defect (VSD). Thirty-two patients who did not have SHDs were designated as the negative control group. RESULTS: The sensitivity and specificity of the TTE-guided 3DPM were greater than or equal to those of the 3DTTE. The P-value of the McNemar test of 3DTTE was >.05, which indicates that the difference was not statistically significant (Kappa = 0.745, P < .001). The P-value of the McNemar test of TTE-guided 3DPM was >.05, which indicates that the difference was not statistically significant (Kappa = 0.955, P < .001). A comparison of 3DTTE and TTE-guided 3DPM resulted in a P-value >.05, which indicates that the difference was not statistically significant (Kappa = 0.879, P < .001). TTE-guided 3DPM displayed the 3D structure of SHDs and cardiac lesions clearly and was consistent with the intra-operative findings. CONCLUSION: Transthoracic echocardiography-guided three-dimensional printed model (TTE-guided 3DPM) provides essential information for preoperative evaluation and decision making for patients with SHDs.

[Endemic plants for medicine use in China].

Based on plant species databases, species lists and literature records, general situation of the Chinese medicinal endemic plant (vascular plant) has been systematically summarized, and its quantity and distribution characteristics of Chinese medicinal endemic plants are presented in this paper. The results showed that 3 150 endemic species are Chinese medicinal plants belonging to 785 genera in 153 families, which includes 38 species of 22 genera in 12 families of pteridophyta, 42 species of 14 genera in7 families of gymnosperms, and 3 070 species of 749 genara in 134 families of angiosperms. The top four families involving medicinal endemic species are Asteraceae (218 species), Ranunculaceae (182 species), Labiatae (151 species), and Liliaceae (133 species). The top four provincial administration distributed medicinal endemic species are Sichuan (1 568 species), Yunnan (1 533 species), Guizhou (955 species) and Hubei (930 species).On the regional scale, the most abundant one is the southwest region (2 465 species), followed by the central region (1 226 species) and the northwest region (949 species). Localization characteristics for domestication and artificial cultivation of medicinal endemic species are more prominent due to their narrower and limited distribution areas, indicating it is possible for these species acting as local potential resource for reasonable economic development.

Comparative proteomic analysis for assessment of the ecological significance of maize and peanut intercropping.

Intercropping is an important and sustainable cropping practice in agroecosystems. Peanut/maize intercropping is known to improve the iron (Fe) content of peanuts in calcareous soils. In this study, a proteomic approach was used to uncover the ecological significance of peanut/maize intercropping at the molecular level. We demonstrate that photosynthesis-related proteins accumulated in intercropped peanut leaves, suggesting that the intercropped peanuts had a stronger photosynthetic efficiency. Moreover, stress-response proteins displayed elevated expression levels in both peanut and maize in a monocropping system. This indicated that intercropping contributes to resistance to stress conditions. Allene oxide synthase and 12-oxo-phytodienoic acid reductase, two key enzymes in jasmonate (JA) biosynthesis, increased in abundance in the maize roots of the intercropping system, consistent with the upregulation of JA-induced proteins shown by microarray analysis. These results imply that JA may act as a signaling molecule, playing an important role in intercropping through rhizosphere interaction. This study suggests that peanut/maize intercropping results in high Fe availability in the rhizosphere, leading to variation in the proteins related to carbon and nitrogen metabolism. The advantages of intercropping systems may improve the ecological adaptation of plants to environmental stress.

[Review of traditional Chinese medicine processed by fermentation].

The fermentation processing of traditional Chinese medicines (TCMs), as an important processing method for TCM, originated from the ancient brewing technology. It has a long history in China. Fermented TCMs (FTCMs) are widely applied among folks for preventing and treating many diseases. There are many kinds of TCM processed by spontaneous fermentation, including Massa Medicata Fermentata, Rhizoma Pinelliae Fermentata, Red fermented rice, Semen Sojae Praepaaratum, Mass Galla chinesis et camelliae Fermentata and Pien Tze Huang. This essay summarizes historical origin, main varieties, the effect of microbial strains, current processing techniques and existing problems of FTCM, and look into the prospect of modern development of FTCMs.

Women's programs versus mixed-gender day treatment: results from a randomized study.

AIMS: To compare outcomes and costs of out-patient women's treatment to mixed-gender programs. DESIGN: Randomized clinical trial. SETTING: Northern California (USA). INTERVENTION: Day treatment: one community-based women's program, two mixed-gender community-based programs and one mixed-gender hospital-based program. PARTICIPANTS: Substance-dependent women recruited from the community (n = 122). MEASUREMENTS: Women were interviewed at baseline, at the end of treatment (94% response rate) and at 6 and 12 months post-treatment (100% response rates). Measures included alcohol and drug use, and psychiatric and social problems. Program costs were estimated using the Drug Abuse Treatment Cost Analysis Program. FINDINGS: No significant differences between the women's program and any of the mixed-gender programs were found for psychiatric problem severity, problems with family and friends or rates of drug use at any of the follow-up points. Rates of alcohol abstinence and total abstinence were similar between the women's program and both of the mixed-gender community programs, but were higher at the mixed-gender hospital program. Only one of these results was replicated in the multivariate analysis, with the odds of total abstinence significantly lower for those randomized to the women's program than the mixed-gender hospital program. However, the average cost of a treatment episode was significantly higher at the hospital program than at the women's program (1212 US dollars versus 543 US dollars). CONCLUSIONS: These findings suggest that female substance abusers may be treated as effectively in mixed-gender programs as in women's programs.

[Mechanism analysis of optimized model of conversion from farmland to forestland in the hill-gully sub-region of Loess Plateau].

Conversion from Farmland to Forestland Program (CFF) is one of the six great ecological forest programs in China. This study covered the CFF model area of the hilly-gully sub-region of loess plateau, and introduced system dynamics and other latest theories and methodologies. Based on the analysis of five modules including that of the site observation of field stations and extensive investigations, and over 10000 original data obtained in the fields of natural science, social science and economics, the operational mechanism of the optimized model was studied. The optimized operational models integrated maximized ecological, economic and social benefits, while sustainability concepts were proposed for typical CFF sites: The Pinus tabulaeformis + Platycladus orientalis + Zanthoxylum spp. + Robinia pseudoacacia model at the eroded flat ridges of the middle reaches of the Yellow River. The result showed that the ecological, economic and social benefits of the optimized model reflected by main indexes were the best or better, and in the other models, either individual one was the best or others were not. From the viewpoint of comprehensive comparison of three great benefits, the optimized model was most excellent, and had eminent difference comparing to other ones through F test. The relationship between ecological and social benefit was eminent positive correlative. Social benefit was the same with economical one at some degrees. The relationship between ecological and economical benefit was more complicated. On the whole, they were positive correlative, but the economical benefit was not the greatest when the ecological one was the greatest. In general, from the viewpoint of largest comprehensive benefit, the three great benefits were not all the best, indicating that the combination of the modules must be reasonable. In order to achieve the ultimate goal of CFF, we must choose the optimized combination of ecological, economical and social benefits, and can't only pursue any one maximum of three great benefits.