Validity of Mobility-Based Exposure Assessment of Air Pollution: A Comparative Analysis with Home-Based Exposure Assessment.

Air pollution exposure is typically assessed at the front door where people live in large-scale epidemiological studies, overlooking individuals' daily mobility out-of-home. However, there is limited evidence that incorporating mobility data into personal air pollution assessment improves exposure assessment compared to home-based assessments. This study aimed to compare the agreement between mobility-based and home-based assessments with personal exposure measurements. We measured repeatedly particulate matter (PM2.5) and black carbon (BC) using a sample of 41 older adults in the Netherlands. In total, 104 valid 24 h average personal measurements were collected. Home-based exposures were estimated by combining participants' home locations and temporal-adjusted air pollution maps. Mobility-based estimates of air pollution were computed based on smartphone-based tracking data, temporal-adjusted air pollution maps, indoor-outdoor penetration, and travel mode adjustment. Intraclass correlation coefficients (ICC) revealed that mobility-based estimates significantly improved agreement with personal measurements compared to home-based assessments. For PM2.5, agreement increased by 64% (ICC: 0.39-0.64), and for BC, it increased by 21% (ICC: 0.43-0.52). Our findings suggest that adjusting for indoor-outdoor pollutant ratios in mobility-based assessments can provide more valid estimates of air pollution than the commonly used home-based assessments, with no added value observed from travel mode adjustments.

Estuarine environmental flow assessment based on the flow-ecological health index relation model: a case study in Yangtze River Estuary, China.

Environmental flow (e-flow) is the water demand of one given ecosystem, which can become the flow regulation target for protection and restoration of river or estuarine ecosystems. In this study, an e-flow assessment based on the flow-ecological health index (EHI) relation model was conducted to improve ecosystem health of the Yangtze River Estuary (YRE). Monitoring data of hydrology, biology, and water environment in the last decades were used for the model establishment. For the description of the YRE ecosystem, an EHI system was developed by cumulative frequency distribution curves and adaption of national standards. After preprocessing original flow values into proportional flow values, the generalized additive model and Monte Carlo random sampling were used for the establishment of the flow-EHI relation model. From the model calculation, the e-flow assessment results were that, in proportional flow values, the suitable flow range was 1.05-1.35, and the optimum flow range was 1.15-1.25 (flows in Yangtze River Datong Station). For flow regulation in two crucial periods, flows of 42,630-65,545 m3/s or over 14,675 m3/s are needed for the suitable flow of YRE in summer (June-August) or January, respectively. An adaptive management framework of ecological health-based estuarine e-flow assessment for YRE was contrived due to the limitation of current established model when facing the extreme drought in summer, 2022. The methodology and framework in this study are expected to provide valuable management and data support for the sustainable development of estuarine ecosystems and to bring inspiration for further studies at even continental or global levels.

Prognostic Value of Segmental Strain After ST-Elevation Myocardial Infarction: Insights From the EARLY Assessment of MYOcardial Tissue Characteristics by Cardiac Magnetic Resonance (EARLY-MYO-CMR) Study.

BACKGROUND: The prognostic value of left ventricular segmental strain (SS) in ST-elevation myocardial infarction (STEMI) remains unclear. HYPOTHESIS: To assess the prognostic value and application of SS. STUDY TYPE: Retrospective analysis of a prospective registry. POPULATION: Five hundred and forty-four patients after STEMI (500 in Cohort 1, 44 in Cohort 2). FIELD STRENGTH/SEQUENCE: 3 T, balanced steady-state free precession, gradient echo, and gradient echo contrast-enhanced images. ASSESSMENT: Participants underwent cardiac MR during the acute phase after STEMI. Infarct-related artery (IRA) strain was determined based on SS obtained from cine images. The primary endpoint was the composite of major adverse cardiovascular events (MACEs) after 8 years of follow-up. In Cohort 2, SS stability was assessed by MR twice within 8 days. Contrast and non-contrast risk models based on SS were established, leading to the development of an algorithm. STATISTICAL TEST: Student's t-test, Mann-Whitney U-test, Cox and logistic regression, Kaplan-Meier analysis, net reclassification index (NRI). P < 0.05 was considered significant. RESULTS: During a median follow-up of 5.2 years, 83 patients from Cohort 1 experienced a MACE. Among SS, IRA peak circumferential strain (IRA-CS) was an independent factor for MACEs (adjusted hazard ratio 1.099), providing incremental prognostic value (NRI 0.180, P = 0.10). Patients with worse IRA-CS (>-8.64%) demonstrated a heightened susceptibility to MACE. Additionally, IRA-CS was significantly associated with microvascular obstruction (MVO) (adjusted odds ratio 1.084) and infarct size (r = 0.395). IRA-CS showed comparable prognostic effectiveness to global peak circumferential strain (NRI 0.100, P = 0.39), also counterbalancing contrast and non-contrast risk models (NRI 0.205, P = 0.05). In Cohort 2, IRA-CS demonstrated stability between two time points (P = 0.10). Based on risk models incorporating IRA-CS, algorithm "HJKL" was preliminarily proposed for stratification. DATA CONCLUSIONS: IRA-CS is an important prognostic factor, and an algorithm based on it is proposed for stratification. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

A detour for snacks and beverages? A cross-sectional assessment of selective daily mobility bias in food outlet exposure along the commuting route and dietary intakes.

The evidence of selective daily mobility bias distorting exposure-health associations is limited. Using 7-day smartphone-based global positioning system (GPS) tracking data for 67 Dutch adults aged 25-45, we conducted paired Wilcoxon tests to compare the absolute and relative exposure to food outlets along actual and modelled commuting routes. We fitted Tobit regressions to examine their associations with three daily snack and soft drink intake outcomes. We found significant differences in absolute food outlet exposure between two types of routes. Adjusted regression analyses yielded unexpected associations between dietary intakes and food outlet exposures. Our results suggested no evidence of a selective daily mobility bias in the association between the food environment along commuting routes and adults' snacks and soft drink consumption in this sample.

Ambient NO2 hinders neutrophil extracellular trap formation in rats: Assessment of the role of neutrophil autophagy.

NO2 has been known to impair immunity and exacerbate susceptibility to infectious diseases. However, scant notice has been taken of the effect of NO2 on neutrophils. Neutrophil extracellular traps (NETs) formation is necessary for NETosis development by neutrophils as an immune system against pathogens. By analyzing the morphology and signature components of NETs, we focused for the first time on finding that 10 ppm of NO2 exposure for 15 consecutive days can hinder the formation of NETs. Next, we used NO2 in vivo derivatives to probe the mechanism for NETs formation in vitro. Our findings showed that NO2 suppression of respiratory burst levels and mitogen-activated protein kinase (MAPK)/Phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling was related to NO2 reduction in NETs formation. Inhibition of phorbol myristate acetate (PMA)-induced NETs formation by NO2 hindered autophagy, as evidenced by increased mTOR protein expression, decreased LC3 protein expression, and reduced autophagic vesicles. By activating mTOR-mediated autophagy, rapamycin (Rapa) reduced the inhibition of PMA-induced NETs by NO2. This study will provide valuable insights into the mechanisms of immunotoxicity of NO2, new insights into the etiology of diseases linked to NETs formation, and a theoretical basis for protection against such illnesses.

Burden of liver complications related to non-alcoholic fatty liver disease in China from 2005 to 2019: Observations from the Global Burden of Disease Study, 2019.

AIM: To assess the burden of liver complications related to non-alcoholic fatty liver disease (LC-NAFLD) from 2005 to 2019 in China. MATERIALS AND METHODS: We used data from the Global Burden of Disease, Injuries, and Risk Factors Study, 2019, to present contemporary and varying profiles of China's LC-NAFLD burden. The Joinpoint Regression model and Gaussian process regression were, respectively, used to estimate the annual percentage change in prevalence rates and disability-adjusted life-year (DALY) rates, and the relationship between the sociodemographic index (SDI) and age-standardized rates of LC-NAFLD. RESULTS: In 2019, China had 293.42 million (95% uncertainty interval [UI]: 263.69-328.44) LC-NAFLD cases with a prevalence rate and DALYs of 20.63 (95% UI: 23.09-18.54) per 1000 people and 591.03 thousand (95% UI: 451.25-737.33), respectively. North China had the highest prevalence but the lowest DALYs of LC-NAFLD, whereas Southwest China had the lowest prevalence but the highest DALYs. LC-NAFLD were more common in men than in women (male: female ratio, 1.27) in 2019. From 2005 to 2019, the prevalence of NAFLD cases increased by 68.32% (from 174.32 million in 2005 to 293.42 million in 2019), mainly because of an age-specific prevalence rate increase. CONCLUSION: The LC-NAFLD burden in China is substantial and has increased markedly over the past 15 years. Effective measures for low SDI regions and men are needed to address the rapidly increasing NAFLD burden.

Assessment of intensive care unit-free and ventilator-free days as alternative outcomes in the pragmatic airway resuscitation trial.

OBJECTIVE: We sought to evaluate the utility and validity of ICU-free days and ventilator-free days as candidate outcomes for OHCA trials. METHODS: We conducted a secondary analysis of the Pragmatic Airway Resuscitation Trial. We determined ICU-free (days alive and out of ICU during the first 30 days) and ventilator-free days (days alive and without mechanical ventilation). We determined ICU-free and ventilator-free day distributions and correlations with Modified Rankin Scale (MRS). We tested associations with trial interventions (laryngeal tube (LT), endotracheal intubation (ETI)) using continuous (t-test), non-parametric (Wilcoxon Rank-Sum test - WRS), count (negative binomial - NB) and survival models (Cox proportional hazards (CPH) and competing risks regression (CRR)). We conducted bootstrapped simulations to estimate statistical power. MAIN RESULTS: ICU-free days was skewed; median 0 days (IQR 0, 0), survivors only 24 (18, 27). Ventilator-free days was skewed; median 0 (IQR 0, 0) days, survivors only 27 (IQR 23, 28). ICU-free and ventilator-free days correlated with MRS (Spearman's ρ = -0.95 and -0.97). LT was associated with higher ICU-free days using t-test (p = 0.001), WRS (p = 0.003), CPH (p = 0.02) and CRR (p = 0.04), but not NB (p = 0.13). LT was associated with higher ventilator-free days using t-test (p = 0.001), WRS (p = 0.001) and CRR (p = 0.03), but not NB (p = 0.13) or CPH (p = 0.13). Simulations suggested that t-test and WRS would have had the greatest power to detect the observed ICU- and ventilator-free days differences. CONCLUSION: ICU-free and ventilator-free days correlated with MRS and differentiated trial interventions. ICU-free and ventilator-free days may have utility in the design of OHCA trials.

Effectiveness of a nurse-led coaching of self-care agency intervention for elderly patients with total laryngectomy: study protocol for a randomised controlled trial.

INTRODUCTION: Due to functional defects and structural destruction after total laryngectomy, patients experienced the poor quality of life, especially for elderly. The barriers to accessing self-care in elderly patients were considered to result from complex and multifaceted interactions of biologic and social factors. Therefore, specific efforts to improve elderly patients' quality of life are needed. The purpose of our study is to verify nurse-led coaching of elderly patient self-care approaches, which can reduce logistic burden of patients and obtain the successful functional rehabilitation ultimately. METHODS AND ANALYSIS: Elderly patients (n=60) scheduled for total laryngectomy will be randomly divided into the intervention group and the control group. Patients in the control group received routinely nursing during hospitalisation and thereby at home after discharge received conventional family care without regular supervision of nurses. Patients in the intervention group will receive a series of self-care intervention based on the transtheoretical model during hospitalisation. During home after discharge, nurses will additionally evaluate and supervise the self-care effect of patients. The two groups of patients' self-care agency, self-efficacy, quality of life and nutritional status will be recorded separately at different time points. Primary outcome is the improvement of patients' self-care agency, and secondary outcome is the improvements of patients' self-efficacy, quality of life, nutritional states and 3-month unplanned readmission rate. ETHICS AND DISSEMINATION: The Ethics Committee of Hubei Cancer Hospital has approved this protocol (KYLLBA2020006). The findings of the trial will be disseminated through peer-reviewed journals, national or international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2100043731.

Understanding heterogeneity among individuals who smoke cigarettes and vape: assessment of biomarkers of exposure and potential harm among subpopulations from the PATH Wave 1 Data.

INTRODUCTION: People who both smoke cigarettes and vape are often considered as a homogenous group even though multiple subgroups may exist. We examined biomarkers of exposure (BOE) and biomarkers of potential harm (BOPH) to differentiate between subgroups of people who smoke and vape based on PATH Study Wave 1 (2013-2014) data. METHODS: We compared people who only smoke cigarettes everyday (Group A, n = 2442) and people who only vape everyday (Group C, n = 169) against people who smoke and vape segmented into subgroups of people who frequently smoke and vape (Group B1, n = 169), frequently smoke and infrequently vape (Group B2, n = 678), frequently vape and infrequently smoke (Group B3, n = 57), and infrequently smoke and vape (Group B4, n = 66). Eighteen BOEs (representing exposure to TSNAs, nicotine, heavy metals, PAHs, and volatile organic compounds) and four BOPHs (representing inflammation and oxidative stress) were compared within the subgroups. RESULTS: Levels of many BOEs/BOPHs were higher among Group B2 relative to Groups B1, B3, and B4. Compared to Group A, many BOEs were significantly lower in Groups B3 (15/18) and B4 (17/18), and some BOEs were higher among B2 (4/18). Compared to Group C, significantly lower BOEs were observed for Group B4 (2/18). CONCLUSIONS: Overall, the levels of BOEs and BOPHs in people who smoke and vape are associated with frequency of cigarette smoking. Our findings indicate that not all people who smoke and vape are the same, and tobacco product use frequency should be considered when categorizing people who smoke and vape.

Two-Year Clinical Follow-Up Assessment of the Novel Cingular Surgical Bovine Pericardial Valve.

Objectives: To evaluate the 2-year clinical safety and hemodynamic outcomes of the Cingular bovine pericardial bioprosthesis. Methods: A prospective, multicenter, single-arm trial was conducted in patients who required aortic or mitral valve replacement. From March 2016 to October 2017, 197 patients were implanted with the Cingular bovine pericardial valve at five sites in China. The clinical outcomes and hemodynamic performance were assessed through a 2-year follow-up. Clinical safety events were reviewed by an independent clinical events committee, and echocardiographic data were assessed by an independent core laboratory. Results: The mean age was 66.9 ± 4.9 years. The 2-year survival rate was 96.4%. A complete 2-year clinical follow-up was achieved in 189 of 190 survivors. No case of structural valve deterioration, major perivalvular leak, prosthetic valve endocarditis, or valve-related reoperation was seen. For the aortic valve, the mean pressure gradient observed was 12.5 ± 4.0 mm Hg, and the effective orifice area (EOA) was 2.0 ± 0.3 cm2. For the smaller size aortic valves, 19 mm and 21 mm, respective mean EOA values of 1.7 ± 0.2 cm2 and 1.8 ± 0.2 cm2 were found. The values for mean pressure gradient and mean EOA for mitral bioprostheses were 4.0 ± 1.4 mm Hg and 2.2 ± 0.3 cm2, respectively. There was no significant change between 1-year and 2-year hemodynamic performance. Conclusions: The Cingular bovine pericardial valve showed favorable clinical safety and hemodynamic outcomes over a 2-year follow-up. Further follow-up is required to validate the long-term durability.

The impact of cigarette and e-cigarette use history on transition patterns: a longitudinal analysis of the population assessment of tobacco and health (PATH) study, 2013-2015.

BACKGROUND: Population models have been developed to evaluate the impact of new tobacco products on the overall population. Reliable input parameters such as longitudinal tobacco use transitions are needed to quantify the net population health impact including the number of premature deaths prevented, additional life years, and changes in cigarette smoking prevalence. METHODS: This secondary analysis assessed transition patterns from PATH wave 1 (2013-14) to wave 2 (2014-15) among adult exclusive cigarette smokers, exclusive e-cigarette users, and dual users. Transition probabilities were calculated by taking into account factors including cigarette smoking and e-cigarette use histories and experimental or established use behaviors. Multinomial logistic regression models were constructed to further evaluate factors associated with transition patterns. RESULTS: Differential transition probabilities emerged among study subgroups when taking into account cigarette smoking and e-cigarette use histories and experimental or established use behaviors. For example, overall 45% of exclusive e-cigarette users in wave 1 continued using e-cigarettes exclusively in wave 2. However, we observed approximately 11 to 14% of wave 1 exclusive experimental e-cigarette users continued to use e-cigarette exclusively in wave 2, compared to about 62% of exclusive established e-cigarette users. The history of cigarette smoking and e-cigarette use is another important factor associated with transition patterns. Among experimental e-cigarette users, 7.5% of individuals without a history of cigarette smoking transitioned to exclusive cigarette smoking, compared to 30% of individuals with a history of cigarette smoking. Additionally, 1.3% of exclusive cigarette smokers in wave 1 transitioned to exclusive e-cigarette use, with the highest transition probability (3.7%) observed in the established cigarette smoker with a history of e-cigarette use subgroup. CONCLUSIONS: Product use histories and current use behaviors are important factors influencing transitions between product use states. Given that experimental users' transition behaviors may be more variable and more influenced by tobacco use history, long-term predictions made by population models could be improved by the use of transition probabilities from established users. As transition patterns might be changing over time, long-term transition patterns can be examined through analysis of future waves of PATH data.

Comparing distance and time as driving exposure measures to evaluate fatal crash risk ratios.

BACKGROUND: The use of an appropriate driving exposure measure is essential to calculate traffic crash rates and risks. Commonly used exposure measures include driving distance and the number of licensed drivers. These measures have some limitations, including the unavailability of disaggregated estimates for consecutive years, low data quality, and the failure to represent the driving population when the crash occurred. However, the length of driving time, available annually from the American Time Use Survey (ATUS), can be disaggregated by age, gender, time-of-day, and day-of week, and addresses the temporal discontinuity limitation of driving distance on the United States (U.S.) national scale. OBJECTIVES: The objective of this study is to determine if the length of driving time as a driving exposure measure is comparable to driving distance by comparing distance-based and time-based fatal crash risk ratios by driver age category, gender, time-of-day, and day-of-week. METHODS: The 2016-2017 National Household Travel Survey (NHTS) provided driving distance, and 2016-2017 Fatality Analysis Reporting System provided the number of drivers in fatal crashes. The distributions of driving distance and length of driving time by driver age category (16-24, 25-44, 45-64, and 65 years or older), gender, time-of-day, day-of-week were compared. Two negative binomial regression models were used to compute the distance-based and time-based fatal crash risk ratios. RESULTS: The distributions of driving-distance were not different from the length-of-driving-time distributions by driver age category, gender, time-of-day, and day-of-week. Driving distance and the length of driving time provide similar fatal crash risk ratio estimates. CONCLUSIONS: The length of driving time can be an alternative to driving distance as a measure of driving exposure. The primary advantage of driving time over driving distance is that, starting from 2003, the disaggregated estimates of the length of driving time are available from ATUS over consecutive years, curtailing the discontinuity limitation of driving distance. Furthermore, the length of driving time is related to drivers' perceived risks about their driving conditions and as a result, may be a better exposure measure than driving distance in comparing crash risks between drivers whose likelihood of traveling in hazardous driving conditions (e.g., nighttime) varies substantially.

Physicochemical properties and health risk assessment of polycyclic aromatic hydrocarbons of fragrant rapeseed oils in China.

BACKGROUND: Fragrant rapeseed oil is a type of hot-pressed oil in China. In this study, physicochemical properties, oxidative stability index (OSI), tocopherols, sterols, and polycyclic aromatic hydrocarbons (PAHs) in fragrant rapeseed oils were evaluated. Additionally, the cancer risk assessment pertaining to PAHs in fragrant rapeseed oil was investigated. RESULTS: Acid values (0.64-2.68 mg potassium hydroxide per gram), peroxide values (1.58-4.86 mmol kg-1 ), and color values (R = 2.6-5.8, Y = 35) of fragrant rapeseed oils were all within codex limits. Tocopherols and sterols ranged from 559.5 to 783.7 mg kg-1 and 4412.6 to 7859.8 mg kg-1 respectively. The OSI (110 °C) was between 4.8 and 15.9 h, with an average value of 10.8 h. Mean values of benzo[a]pyrene and PAH4 (chrysene, benz[a]anthracene, benzo[b]fluroranthene, and benzo[a]pyrene) were 2.32 µg kg-1 and 8.21 µg kg-1 respectively. The 95% dietary exposure of benzo[a]pyrene equivalent (BaPeq) contents from PAH4 were 0.3474 ng kg-1 day-1 , 0.3942 ng kg-1 day-1 , 1.8293 ng kg-1 day-1 , and 0.4294 ng kg-1 day-1 for male children, adolescents, adults, and seniors respectively. For females, these values were 0.3443 ng kg-1 day-1 , 0.3228 ng kg-1 day-1 , 1.8697 ng kg-1 day-1 , and 0.4084 ng kg-1 day-1 , respectively. Moreover, incremental lifetime cancer risk values at the cumulative probabilities of 91.3% and 91.6% for male adults and female adults respectively were higher than 1 × 10-5 . CONCLUSION: The results imply that the potential risk of cancer with PAHs in fragrant rapeseed oil should be a concern, especially for the health of adults. Fragrant rapeseed oil is still a product subject to contamination by PAHs. Limits for PAH4 of fragrant rapeseed oil should be included in Chinese regulations to improve safety. © 2020 Society of Chemical Industry.

Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies.

BACKGROUND: Cardiovascular disease (CVD) has become an increasingly common limitation to effective anticancer therapy. Yet, whether CVD events were consistently reported in pivotal trials supporting contemporary anticancer drugs is unknown. OBJECTIVES: The authors sought to evaluate the incidence, consistency, and nature of CVD event reporting in cancer drug trials. METHODS: From the Drugs@FDA, clinicaltrials.gov, MEDLINE, and publicly available U.S. Food and Drug Administration (FDA) drug reviews, all reported CVD events across latter-phase (II and III) trials supporting FDA approval of anticancer drugs from 1998 to 2018 were evaluated. The primary outcome was the report of major adverse cardiovascular events (MACE), defined as incident myocardial infarction, stroke, heart failure, coronary revascularization, atrial fibrillation, or CVD death, irrespective of treatment arm. The secondary outcome was report of any CVD event. Pooled reported annualized incidence rates of MACE in those without baseline CVD were compared with reported large contemporary population rates using relative risks. Population risk differences for MACE were estimated. Differences in drug efficacy using pooled binary endpoint hazard ratios on the basis of the presence or absence of reported CVD were also assessed. RESULTS: Overall, there were 189 trials, evaluating 123 drugs, enrolling 97,365 participants (58.5 ± 5 years, 46.0% female, 72.5% on biologic, targeted, or immune-based therapies) with 148,138 person-years of follow-up. Over a median follow-up of 30 months, 1,148 incidents of MACE (375 heart failure, 253 myocardial infarction, 180 strokes, 65 atrial fibrillation, 29 revascularizations, and 246 CVD deaths; 792 in the intervention vs. 356 in the control arm; p < 0.01) were reported from the 62.4% of trials noting any CVD. The overall weighted-average incidence was 542 events per 100,000 person-years (716 per 100,000 in the intervention arm), compared with 1,408 among similar-aged non-cancer trial subjects (relative risk: 0.38; p < 0.01), translating into a risk difference of 866. There was no association between reporting CVD events and drug efficacy (hazard ratio: 0.68 vs. 0.67; p = 0.22). CONCLUSIONS: Among pivotal clinical trials linked to contemporary FDA-approved cancer drugs, reported CVD event rates trail expected population rates.

Phenotypic assessment and ligand screening of ETA/ETB receptors with label-free dynamic mass redistribution assay.

Endothelin receptors, consisting of two subtypes, ETA and ETB, are expressed in various tissues and widely regulate cardiovascular systems. The two receptors show distinct biological characteristics and are involved in different downstream pathways. Hence, to evaluate the ETA and ETB receptors on the same platform is helpful to display their pharmacological features. In this study, we developed a label-free dynamic mass redistribution (DMR) assay to investigate the phenotypic features of the ETA and ETB receptors in native cell lines. Meanwhile, specific agonists and antagonists were investigated for their pharmacological parameters. Results indicated that the DMR response of endothelin 1 (ET-1, an endogenous ETA/ETB agonist) was cell line dependent on ETA receptors and this ligand generated a biphasic dose-response curve in SH-SY5Y as well as PC3 cell lines. ET-1 and IRL 1620 (an ETB agonist) showed different DMR responses in U251 cells. IC50 values of antagonists were consistent with the Ki values previously reported. Furthermore, a list of compounds was screened on the ETA and ETB receptor models established by the high-throughput DMR assays. This study demonstrated that the DMR assay had great potential in the phenotypic-based investigation and ligand screening of GPCRs.

How would China achieve WHO's target of eliminating HCV by 2030?

Introduction: Hepatitis C virus (HCV) infection is a major global health concern on the rise, prompting unprecedented efforts by the World Health Organization (WHO) to eliminate this epidemic by 2030. Being the country with the largest HCV-infected population in the world, China has been faced with a general lack of awareness for HCV, low treatment uptake and subpar collaborations among healthcare providers and stakeholders. Areas covered: This review discusses the epidemiological situations of HCV infection and the challenges in HCV management in China. This review also explores micro-elimination strategies in China, identifying potential sub-populations for concerted efforts in eliminating HCV. As DAAs are increasingly recognized as a more effective alternative to traditional regimens, the cost-effectiveness and budget impacts of bringing more DAAs into the reimbursement lists are also addressed. Several small-scale targeted literature searches were conducted in PubMed for various topics covered in the article, and hand searching was performed to fill any data gaps. More recent data were used wherever possible. Expert opinion: Considering the unique socioeconomical landscape of China, micro-elimination strategies might be more effective and should be targeted at high-risk populations. Varying regional needs in HCV care across the country necessitate decentralized approaches in research and policy-making.

Assessment of Survival of Pediatric Patients With Hepatoblastoma Who Received Chemotherapy Following Liver Transplant or Liver Resection.

Importance: The incidence of hepatoblastoma is increasing, and liver transplant (LT) provides a potential cure for pediatric patients with unresectable hepatoblastoma; however, the use of LT for hepatoblastoma has not been examined in a modern cohort. Moreover, data are lacking on the association between the type of surgical management received and overall risk of death among pediatric patients with hepatoblastoma. Objectives: To examine the receipt of LT among pediatric patients with hepatoblastoma and to assess overall survival of pediatric patients with hepatoblastoma who were treated with chemotherapy after LT or liver resection (LR) using data from a national cancer registry. Design, Setting, and Participants: This cohort study used data for 443 pediatric patients with histologically confirmed hepatoblastoma who received chemotherapy and surgical therapies, as documented in the Surveillance, Epidemiology, and End Results database of the National Cancer Institute, from 2004 to 2016, with follow-up through December 31, 2018. Multivariable logistic regression was used to determine factors associated with the use of LT. Cox proportional hazards models were used to assess factors associated with overall survival. Data analysis was performed from April 18, 2019, to July 25, 2019. Main Outcomes and Measures: Overall survival. Results: Among 443 patients receiving chemotherapy (mean [SD] age, 1.8 [2.6] years; 167 [37.7%] female), 350 (79%) underwent LR and 93 (21%) underwent LT. Multivariable analysis showed that patients with multiple lesions were more likely to undergo LT than LR (31% vs 13%; P < .001) and that patients with higher stage tumors were more likely to undergo LT than LR (local disease, 20% vs 58%; regional disease, 58% vs 24%; distant disease, 22% vs 18%; P < .001). There was a statistically significant 19% increase in the receipt of LT from 8% in 1998 to 27% 2016 (trend test, P = .02). Overall survival at 10 years was not significantly different for the 2 surgical management strategies (87.2% [95% CI, 78.3%-97.1%] for patients undergoing LT vs 87.8% [95% CI, 83.5%-92.4%] for those undergoing LR; P = .92). The overall risk of death was not significantly different for LT compared with LR (hazard ratio, 0.716; 95% CI, 0.309-1.657; P = .44). Conclusions and Relevance: The use of LT for the management of hepatoblastoma has increased significantly over time. Among pediatric patients with hepatoblastoma receiving chemotherapy, LT was not associated with improved overall survival compared with LR. There was no significant different between treatments with regard to the outcome variable, but this finding cannot be interpreted as indicating equivalence or lack of superiority.

An Assessment of Upper Limits of Normal for ALT and the Impact on Evaluating Natural Course of Chronic Hepatitis B Virus Infection in Chinese Children.

BACKGROUND: The current upper limits of normal (ULN) for serum alanine aminotransferase (ALT) are increasingly challenged. We aimed to re-evaluate the ULN for ALT and assess the potential impact on the classification of natural course of chronic hepatitis B virus (HBV) infection in children. METHODS: Laboratory data obtained from three hospitals in China were retrospectively analysed. In total, 2054 children with chronic HBV infection and 8149 healthy children at age ≤18 years were included in the study. RESULTS: Age-specific and gender-specific ULNs for ALT, at averages of 30 U/L for boys and 24 U/L for girls, were calculated from the data of healthy children. Using the revised ULNs vs. the current ULNs (40-50 U/L), 31-60% vs. 9-17% of the 2054 HBV-infected children had an abnormal result as seen in their ALT baseline analysis, and the highest abnormality rate was seen in the infants. Data of 516 HBV-infected children were applied for the classification of clinical phase, 28.8% vs. 19.8% of the children were classified into the phases of hepatitis B e antigen (HBeAg-)positive/negative hepatitis. During a median follow-up of 62 months, 39 of 153 children underwent HBeAg seroconversion, whereas 3 of them had persistently "normal" ALT, according to the current ULN. CONCLUSIONS: The revision of ULN for ALT in children substantially impacts the classification of the natural course of chronic HBV infection. Mild ALT fluctuation is common during the stage childhood, suggesting a need to rethink the current conceptions of immune tolerance and natural course of chronic HBV infection in the children.

A cross-sectional assessment of health-related quality of life in Chinese patients with chronic hepatitis c virus infection with EQ-5D.

BACKGROUND: Hepatitis C virus (HCV) infection is one of the most common liver infections, with a decrement in HRQoL of HCV patients. This study aims to assess Health-related quality of life (HRQoL) in Chinese patients with chronic HCV infection, and to identify significant predictors of the HRQoL in these patients of China. METHODS: In this cross-sectional observational study, treatment-naïve Han ethnic adults with chronic HCV infection were enrolled. Adopting European Quality of Life scale (EQ-5D) and EuroQOL visual analogue scale (EQ-VAS) were used to qualify HRQoL. Results were reported in descriptive analyses to describe sociodemographic and clinical characteristics. Multiple linear regression analysis was applied to investigate the associations of these variables with HRQoL. Binary logistic regression analysis was performed to identify associations of these variables with HRQoL by dimensions of EQ-5D. RESULTS: Nine hundred ninety-seven patients were enrolled in the study [median age 46.0 (37.0, 56.0) years; male 54.8%]. Mean EQ-5D index and EQ-VAS score were 0.780 ± 0.083 and 77.2 ± 14.8. Multiple Linear regression analysis showed that income (< 2000 RMB, ß = - 0.134; 2000-4999 RMB, ß = - 0.085), moderate or severe symptoms of discomfort (more than one symptoms, ß = - 0.090), disease profile (cirrhosis, ß = - 0.114), hyperlipidemia (ß = - 0.065) and depression (ß = - 0.065) were independently associated with EQ-5D index. Residence (the west, ß = 0.087), income (< 2000 RMB, ß = - 0.129; 2000-4999 RMB, ß = - 0.052), moderate or severe symptoms of discomfort (more than one symptoms, ß = - 0.091), disease profile and depression (ß = - 0.316) were the influencing factors on EQ-VAS. Binary logistic regression indicated that disease profile and clinical depression were the major influencing factors on all five dimensions of EQ-5D. CONCLUSIONS: In this cross-sectional assessment of HCV patients in China, we indicated HRQoL of Chinese HCV patients. Significant negative associations between HRQoL and sociodemographic and clinical factors such as moderate or severe symptoms of discomfort, disease profile and depression emerged. We have to focus on optimally managing care of HCV patients and improving their HRQoL. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01293279. Date of registration: February 10, 2011.