A Rapid, Sensitive, and High-throughput Method for the Simultaneous Determination of Antihypertensive Drug Combinations in Dog Plasma by UHPLC-MS/MS: The Assessment of Predicable Bioequivalence of In-vitro Dissolution Condition.

BACKGROUND: Essential hypertension is a common clinical disease and a risk factor for cardiovascular and cerebrovascular diseases. Olmesartan medoxomil, amlodipine, and hydrochlorothiazide are commonly used antihypertensive drugs. The aim of this study was to establish a robust UPLC-MS/MS method for the simultaneous determination of olmesartan medoxomil, amlodipine, and hydrochlorothiazide in dog plasma. At the same time, the release in vivo and in vitro studies were conducted, and a preliminary in vitro-in vivo correlation (IVIVC) evaluation was performed. METHODS: The bioequivalence experiment was conducted with a double-crossed design. Three major components were extracted and analyzed by UHPLC-MS/MS. With the MRM scan, olmesartan and amlodipine were quantified by fragment conversion (m/z 447.10→190.10) and (m/z 408.95→294.00) under positive ESI mode, while hydrochlorothiazide was quantified with fragment conversion (m/z 295.90→268.90) under negative ESI mode. The in vitro release studies were performed using a USP paddle, and the dissolution medium was chosen from pH 6.0 to pH 6.8 according to the BCS classification of compounds. The IVIVC was calculated using the Wagner-Nelson equation. RESULTS: The linear ranges of olmesartan, amlodipine, and hydrochlorothiazide in the plasma were 5.0-2500, 0.1-50, and 3.0-1500 ng/mL, respectively. All accuracies were within 3.8% of the target values, and the findings revealed that intra-day and inter-day accuracy was less than 12.1%. Moreover, the recoveries exceeded 88.3%, the matrix effect tests were positive, and the stability tests were positive. With the establishment of correlation, the distinguishable dissolution condition (pH 6.8) was selected as the predictable condition. CONCLUSION: The established method was suitable for the preclinical pharmacokinetic study of tripartite drugs with strong specificity and high sensitivity. Through the evaluation of IVIVC, the connection between in vivo and in vitro drug testing was initially established.

The impact of regional policy implementation on the decoupling of carbon emissions and economic development.

The contradiction between economic growth demands and the achievement of the "dual-carbon" goals at the regional level is a pressing issue in China. As a significant economic and cultural center in the western region of China, the Guanzhong Plain urban agglomeration has experienced rapid development and urbanization, making it one of the key areas for national development. Therefore, greater attention should be given to carbon emission reduction in this region. This study focuses on the dataset from 2010 to 2019 in the Guanzhong Plain urban agglomeration, utilizing an input-output table to construct a carbon dioxide emission inventory. The research investigates the impact of regional classification on carbon emission levels within the Guanzhong Plain urban agglomeration. Furthermore, the Tapio decoupling analysis method is employed to assess the decoupling coefficient between regional economic development and carbon emissions. Additionally, the Theil index inequality analysis method is utilized to measure the disparities in per capita carbon emissions among cities within the region. Research findings indicate the following: 1) The regional classification of the Guanzhong Plain urban agglomeration is an effective policy for reducing regional carbon emissions and promoting carbon emissions reduction. 2) There exist variations in energy and industrial structures among cities within the urban agglomeration, necessitating tailored measures for low-carbon transition based on the specific circumstances of each city. 3) The regional classification of the urban agglomeration significantly influences the degree of decoupling between economic development and carbon emissions, with a trend towards stronger decoupling. The study suggests that cities within the Guanzhong Plain urban agglomeration should adopt measures aligned with their natural conditions and economic characteristics to achieve a low-carbon transition. Leveraging the regional cooperation capacity of the urban agglomeration is crucial to decouple economic development from carbon emissions, thereby promoting sustainable economic growth and environmental protection in a mutually beneficial manner.

Assessment of plasma amino acids, purines, tricarboxylic acid cycle metabolites, and lipids levels in NSCLC patients based on LC-MS/MS quantification.

Non-small cell lung cancer (NSCLC) is the most common type of malignant tumor of the lung with poor prognosis. Currently, there is still no effective strategy for diagnosing lung cancer from the perspective of multiple biomarkers containing both polar and nonpolar molecules. In order to explore the pathological changes of NSCLC at the endogenous molecule levels, and further establish the strategy for identifying and monitoring drug efficacy of NSCLC, targeted metabolomics and lipidomics studies were established with NSCLC patients. Polar metabolites including 21 amino acids, 7 purines, 6 tricarboxylic acid (TCA) cycle metabolites, and nonpolar lipids like phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), sphingomyelin (SM), and ceramide (Cer), diacylglycerol (DG), triacylglycerol (TG), were quantitatively determined based on LC-MS/MS, taking into account their metabolism were significantly concerned with the occurrence of lung cancer in previous study. As a result, 14 polar metabolites and 16 lipids were prominently altered in the plasma of NSCLC patients, among which, after multivariate statistical analysis, LPC 18:0 (sn-2), L-Phenylalanine (Phe), oxaloacetic acid (OAA) and xanthine (XA) were screened out as potential small molecules and lipid biomarkers for NSCLC. Furthermore, a new strategy for formulating equation of NSCLC identification was proposed and clinical utility was successfully evaluated through Kangai injection treatment to NSCLC patients. Taking together, this study investigated the pathological changes of NSCLC from the perspective of endogenous polar and nonpolar molecules, and shed a light on identification of NSCLC.

The Role of Housing Tenure Opportunities in the Social Integration of the Aging Pre-1970 Migrants in Beijing.

This study focuses on the social integration of the pre-1970 first-generation migrants in reformist China, who were born before the year 1970 while getting old in the destination cities. The pre-1970 first-generation migrants are not a homogeneous group but are composed of: (a) those over 45 years old and still working but facing age discrimination; and (b) the elderly granny as nanny assuming the domestic and child-care work for their sons or daughters in the destination cities. We conceptualized and re-defined the aging migrants' social integration into three dimensions (i.e., participation practices, communication contacts, and subjective perceptions), and used the 2017 Migrant Dynamics Monitoring Survey (MDMS) data from Beijing to measure and explain the varied integration levels among a total of 1267 aging migrant samples in the Beijing metropolis. It is proven that housing tenure matters and housing tenure entitlement would be conductive to beefing up aging migrants' integration. However, informal housing should not be "stigmatized" as a segregated world, since those dwelling in the informal housing have reported a higher probability of perceiving a fully integrated status (namely subjective well-being, SWB) than those living in the dormitory-like housing. Additionally, an employment-income paradox is found, which shows that higher economic achievement is NOT equivalent to a higher social integration status for the aging migrants.

Effects of prenatal polycyclic aromatic hydrocarbons and childhood material hardship on reading achievement in school-age children: A preliminary study.

Background: Children from socioeconomically disadvantaged backgrounds are at elevated risk for reading problems. They are also likely to live in neighborhoods with high levels of air pollution and to experience material hardship. Despite these risk factors, the links between prenatal chemical exposures, socioeconomic adversities, and reading problems in youth from disadvantaged backgrounds remain understudied. Here we examine associations between prenatal exposure to polycyclic aromatic hydrocarbons (PAH), a common air pollutant, and reading skills, and determine if this relationship is exacerbated by material hardship among Black and/or Latinx children who have been followed as part of a longitudinal urban birth cohort. Methods: Mothers and their children, who were participants in a prospective birth cohort followed by the Columbia Center for Children's Environmental Health, were recruited for the current study. Personal prenatal PAH exposure was measured during the third-trimester of pregnancy using a personal air monitoring backpack. Mothers reported their level of material hardship when their child was age 5 and children completed measures of pseudoword and word reading [Woodcock Johnson III Tests of Achievement (WJ-III) Basic Reading Index] at age 7. We used multiple linear regression to examine the effects of the interaction between prenatal PAH and material hardship on Basic Reading Index, controlling for ethnicity/race, sex, birthweight, presence of a smoker in the home (prenatal), and maternal education (prenatal) (N = 53). Results: A prenatal PAH × material hardship interaction significantly associated with WJ-III Basic Reading Index scores at age 7 (ß = -0.347, t(44) = -2.197, p = 0.033). Exploratory analyses suggested that this effect was driven by untimed pseudoword decoding (WJ-III Word Attack: ß = -0.391, t(44) = -2.550, p = 0.014). Conclusion: Environmental chemical exposures can be particularly toxic during the prenatal period when the fetal brain undergoes rapid development, making it uniquely vulnerable to chemical perturbations. These data highlight the interactive effects of environmental neurotoxicants and unmet basic needs on children's acquisition of reading skill, specifically phonemic processing. Such findings identify potentially modifiable environmental risk factors implicated in reading problems in children from economically disadvantaged backgrounds.

Regional Differences in Hospital Costs of Acute Ischemic Stroke in China: Analysis of Data From the Chinese Acute Ischemic Stroke Treatment Outcome Registry.

Background and Purpose: Studies on the regional differences in hospital costs of acute ischemic stroke (AIS) are scarce in China. We aimed to explore the regional differences in hospital costs and identify the determinants of hospital costs in each region. Methods: Data were collected from the Chinese Acute Ischemic Stroke Treatment Outcome Registry (CASTOR), a multicenter prospective study on patients diagnosed with AIS and hospitalized from 2015 to 2017. Univariate and multivariate analyses were undertaken to identify the determinants of hospital costs of AIS. Results: A total of 8,547 patients were included in the study, of whom 3,700 were from the eastern area, 2,534 were from the northeastern area, 1,819 were from the central area, and 494 were from the western area. The median hospital costs presented a significant difference among each region, which were 2175.9, 2175.1, 2477.7, and 2282.4 dollars in each area, respectively. Each region showed a similar hospital cost proportion size order of cost components, which was Western medicine costs, other costs, diagnostic costs, and traditional medicine costs, in descending order. Male sex, diabetes mellitus, severe stroke symptoms, longer length of stay, admission to the intensive care unit, in-hospital complications of hemorrhage, and thrombectomy were independently associated with hospital costs in most regions. Conclusion: Hospital costs in different regions showed a similar proportion size order of components in China. Each region had different determinants of hospital costs, which reflected its current medical conditions and provided potential determinants for increasing medical efficiency according to each region's situation.

An IoT-Based Life Cycle Assessment Platform of Wind Turbines.

Life cycle assessment (LCA) is conducive to the change in the wind power industry management model and is beneficial to the green design of products. Nowadays, none of the LCA systems are for wind turbines and the concept of Internet of Things (IoT) in LCA is quite a new idea. In this paper, a four-layer LCA platform of wind turbines based on IoT architecture is designed and discussed. In the data transmission layer, intelligent sensing of wind turbines can be achieved and their status and location can be monitored. In the data transmission layer, the LCA platform can be effectively integrated with enterprise information systems through the object name service (ONS) and directory service (DS). In the platform layer, a model based on IMPACT 2002+ is developed, and four management modules are designed. In the application layer, different from other systems, energy payback time (EPBT) is selected as an important evaluation index for wind turbines. Compared with the existing LCA systems, the proposed system is specifically for wind turbines and can collect data in real-time, leading to improved accuracy and response time.

Geographic information system-based health risk assessment of rural drinking water in Central China: a case study of You County, Hunan.

This study assessed potential human health hazards posed by drinking water from centralized water supply systems in rural You County, along with its spatial distribution. While most previous studies have focused on source water or urban drinking water, this study evaluated the health risk posed by 20 common pollutants (arsenic, cadmium, chromium(VI), lead, mercury, selenium, cyanide, fluoride, nitrate nitrogen, trichloromethane, tetrachloromethane, chlorite, aluminum, iron, manganese, copper, zinc, ammonia nitrogen, chlorine dioxide, and volatile phenols) in rural terminal tap water. The assessment adopted the model recommended by the US Environmental Protection Agency (EPA) and was combined with the geographic information system (GIS) analysis to explore the spatial distribution of risk factors. Water samples were collected from 13 townships in You County across four quarters of 2019. The results indicated that the average carcinogenic risk of the rural drinking water was 2.45 × 10-5, ranging from 1.80 × 10-5 to 3.89 × 10-5, which never exceeded the maximum acceptable range recommended by the US EPA (1.0 × 10-4 ~ 1.0 × 10-6). The average hazard index (HI), which reflects noncarcinogenic risk levels, was 0.75 and ranged from 0.34 to 1.74. Throughout the year, some townships presented HI > 1, indicating a non-carcinogenic risk. The GIS analysis indicated that noncarcinogenic risks were mainly distributed in the north, followed by the east and west. This is generally consistent with the spatial distribution of chlorite concentrations, which contribute most strongly to noncarcinogenic risk levels. The northern You County should therefore be prioritized for health risk control, followed by the eastern and western regions. Chlorite is the priority pollutant for control.

Occupational Health and Safety Risk Assessment based on Combination Weighting and Uncertain Linguistic Information: Method Development and Application to a Construction Project.

OCCUPATIONAL APPLICATIONSOccupational hazards and work-related accidents are a substantial problem in countries around the world. Therefore, it is of great importance to develop appropriate techniques to assess and reduce the risk of occupational hazards. In many situations, however, exact data are inadequate to model real-life scenarios, because of the complexity of occupational health and safety (OHS) risk assessment problems. We present a new OHS risk assessment model to assess and rank the risk of occupational hazards based on combination weighting and uncertain linguistic information. Moreover, a practical example of a shopping mall construction project is given to illustrate the effectiveness of the proposed model. The new model was found to provide a useful, practical, and flexible way for risk evaluation in OHS. In particular, it offered a new method for capturing domain expert opinions and prioritizing potential occupational hazards to improve the health and safety of workers.

TECHNICAL ABSTRACTBackground OHS is an important issue, since it has great impact on the cost, productivity, and social reputation of a company. Occupational hazards have attracted considerable attention from both researchers and practitioners, because they can cause financial and personal loss as well as intangible damage within organizations and enterprises worldwide.Purpose Our aim was to develop a new model to assess and rank the risk of occupational hazards and identify high-risk ones for the promotion of occupational health.Methods The q-rung orthopair uncertain linguistic sets (q-ROULSs) are utilized to deal with uncertain risk assessment information provided by experts. An extended evaluation based on distance from average solution (EDAS) method is introduced to determine the risk priorities of occupational hazards. Moreover, a combination weighting method is adopted to derive the relative weights of risk criteria. A case study, involving a shopping mall construction project, was used to illustrate the applicability and validity of the proposed model.Results Ten occupational hazards were identified and, according to the proposed model, their risk priority scores were determined. From these scores, three hazards were determined as the most serious (i.e., collision with immobile objects or being struck by moving objects; fall of a person from height; and trapping, being crushed-inside or between objects). Conclusions: The proposed model was found to be a reliable and practical tool for the risk assessment of occupational hazards in OHS. It can depict the uncertain risk assessments of experts in a more prominent manner, and produce a reliable risk ranking of occupational hazards for corrective actions.

Qualitative and quantitative assessment of posterior segment optical coherence tomography images using standard photos: the Liwan Eye Study.

BACKGROUND/AIMS: To develop a standardised grading scheme, using standard photos, for spectral-domain ocular coherence tomography (SD-OCT) images of the posterior eye and evaluate the interobserver agreement among trained ophthalmologists in identifying pathological changes. METHODS: Subjects were recruited from Liwan District, Guangzhou, with SD-OCT data collection from June 2013 to November 2013 as part of 10-year follow-up visits from the Liwan Eye Study. All subjects underwent SD-OCT imaging of the macula with scanning lines analysed by two ophthalmologists to assess for the presence of 12 different posterior segment lesions. Per cent agreement for each lesion between the graders and quantitative measures of dome-shaped macula (DSM) height and choroidal thickness were calculated. RESULTS: A total of 679 SD-OCT images from 679 subjects were independently evaluated by the two graders. Each of the 12 lesions was successfully graded as present or absent in over 96% of images. For all lesions, per cent agreement between observers was over 90%, ranging from 90.7% for epiretinal membranes and retinal pigment epithelium thickenings to 99.7% for full thickness macular holes and retinal detachments. Quantitative measurements of DSM height and choroidal thickness at three locations of the eye all exhibited intraclass correlation scores between the two graders of greater than 0.9. CONCLUSION: Our study demonstrates high concordance between graders in characterising posterior segment lesions using SD-OCT images, validating the continued use of this imaging modality in the diagnosis of posterior eye disease.

Quality assessment of Herba Leonuri based on the analysis of multiple components using normal- and reversed-phase chromatographic methods.

A novel, improved, and comprehensive method for quality evaluation and discrimination of Herba Leonuri has been developed and validated based on normal- and reversed-phase chromatographic methods. To identify Herba Leonuri, normal- and reversed-phase high-performance thin-layer chromatography fingerprints were obtained by comparing the colors and Rf values of the bands, and reversed-phase high-performance liquid chromatography fingerprints were obtained by using an Agilent Poroshell 120 SB-C18 within 28 min. By similarity analysis and hierarchical clustering analysis, we show that there are similar chromatographic patterns in Herba Leonuri samples, but significant differences in counterfeits and variants. To quantify the bio-active components of Herba Leonuri, reversed-phase high-performance liquid chromatography was performed to analyze syringate, leonurine, quercetin-3-O-robiniaglycoside, hyperoside, rutin, isoquercitrin, wogonin, and genkwanin simultaneously by single standard to determine multi-components method with rutin as internal standard. Meanwhile, normal-phase high-performance liquid chromatography was performed by using an Agilent ZORBAX HILIC Plus within 6 min to determine trigonelline and stachydrine using trigonelline as internal standard. Innovatively, among these compounds, bio-active components of quercetin-3-O-robiniaglycoside and trigonelline were first determined in Herba Leonuri. In general, the method integrating multi-chromatographic analyses offered an efficient way for the standardization and identification of Herba Leonuri.

Assessment of periodontal mechano-nociceptive function in healthy Chinese individuals.

OBJECTIVE: Few clinical techniques are available for the description of mechano-nociceptive function in human periodontal tissues. The objective of this study was to test a new technique for assessment of periodontal mechano-nociceptive function by direct application of controlled forces to the teeth and quantify site, side and gender differences in healthy individuals. DESIGN: Twenty healthy young adults (ten males and ten females) participated. A handheld pressure algometer was used to assess pressure pain threshold (PPT) on the maxillary and mandibular central incisors, canines and first premolars on the left and the right side from two directions: lateral and vertical. Statistical analysis was performed using analyses of variance (ANOVA) with repeated measures to compare data. RESULTS: There were significant gender differences of PPT for both lateral (Plateral=0.007) and vertical (Pvertical=0.001) directions with lower thresholds in females (higher sensitivity) than in males. A significant site effect (Plateral=0.002, Pvertical<0.001) was observed with less sensitivity at the first premolar compared to the anterior teeth. No significant right-to-left side differences (P=0.082) were found for the PPTs. There were significant PPT differences between maxillary and mandibular teeth (Plateral=0.020, Pvertical=0.041,) and significant differences between lateral and vertical direction (P<0.001). CONCLUSION: The novel application of PPTs directly to the teeth indicated an adequate and practical method with potential value for clinical assessment of painful conditions affecting the periodontal ligament.

Biocompatibility Assessment of Polyethylene Glycol-Poly L-Lysine-Poly Lactic-Co-Glycolic Acid Nanoparticles In Vitro and In Vivo.

The present study was designed to evaluate the biocompatibility of nanoparticles polyethylene glycol (PEG)-poly L-lysine (PLL)-poly lactic-co-glycolic acid copolymer (PLGA) (PEG-PLL-PLGA) before clinical application. We applied some tests to assess the safety of PEG-PLL-PLGA nanoparticles (NPs). There was low cytotoxicity of PEG-PLL-PLGA NPs in vitro as detected by MTT assay. Cell apoptosis and intracellular accumulation of PEG-PLL-PLGA were determined by FCM assay. The apoptotic rate induced by nanoparticles and the fluorescence intensity of intracellular daunorubicin (DNR) demonstrated that DNR-PEG-PLL-PLGA could be taken up by the mouse fibroblast cells (L929 cells). Hemolysis test and micronucleus (MN) assay demonstrated that the nanoparticles have no obviously blood toxicity and genotoxicity. DNR-PEG-PLL-PLGA NPs were injected into mice through tail vein to calculate the median lethal dose (LD50), the results showed that they had a wide safe scale. Blood was taken by removing the eyeball of mice to study the influence of DNR-PEG-PLL-PLGA in hepatic and renal functions. The results revealed that there was no significant difference as compared with the control group. Interestingly, the pathologic changes of heart, liver, spleen, lung and kidney were observed in nanoparticles treated mice. Thus, this study demonstrates that PEG-PLL-PLGA NPs appear to be highly biocompatible and safe nanoparticles that can be suitable for further application in the treatment of tumor.

Individual and combined developmental toxicity assessment of bisphenol A and genistein using the embryonic stem cell test in vitro.

The potential developmental toxicity of environmental estrogenic endocrine disruptors have become a great concern in recent years. In this study, two typical environmental oestrogen, namely, bisphenol A (BPA) and genistein (GEN) were investigated for potential embryotoxicity using the embryonic stem cell test model. Afterwards, a 4×4 full factorial design and the estimated marginal means plot were performed to assess the combined effects of these two compounds. According to the linear discriminant functions and classification criteria, bisphenol A and genistein were classified as weakly embryotoxic and strongly embryotoxic respectively. As for combined effects, the overall interaction between BPA and GEN on embryonic stem cells (ESCs) differentiation was synergistic at low dosages, however, on ESCs and 3T3 cell proliferation, the predominate action was additive. Considering the actual daily intake of these chemicals, it is concluded that BPA alone might not have adverse reproductive or developmental effects on human being. However, given that BPA and GEN do have synergistic effect at low concentration, they may disturb normal embryo development together, which could result in birth defect and behavioral alterations later in life.

The assessment of non-feminizing estrogens for use in neuroprotection.

Menopause is associated with a precipitous decline in circulating estrogens and a resulting loss of the neuroprotective actions of this steroid hormone. In view of the results of the Women's Health Initiative and the preceding knowledge that orally administered estrogens has a variety of adverse side effects, likely through actions on peripheral estrogen receptor alpha (ERα), we initiated a program of research to synthesis and assess a group of non-feminizing estrogens that lack ability to interact with ERs but retain much of the neuroprotective action of feminizing estrogens. This program of research is aimed at the identification of compounds which do not stimulate ERs but are potentially neuroprotective in vitro and in animal models of neuronal cell death. We discovered that the most effective non-feminizing estrogens were those with large bulky groups in the 2 and/or 4 carbon of the phenolic A ring of the steroid. These compounds were 8- to 114-fold more potent than 17 ß-estradiol (ßE2), but lacked ER binding capacity in vitro and feminizing effects in vivo. The success of this program of research suggests that strategies to optimize non-feminizing estrogens for use in postmenopausal women can be successful.