Rapid automated extracellular vesicle isolation and miRNA preparation on a cost-effective digital microfluidic platform.

As a prerequisite for extracellular vesicle (EV) -based studies and diagnosis, effective isolation, enrichment and retrieval of EV biomarkers are crucial to subsequent analyses, such as miRNA-based liquid biopsy for non-small-cell lung cancer (NSCLC). However, most conventional approaches for EV isolation suffer from lengthy procedure, high cost, and intense labor. Herein, we introduce the digital microfluidic (DMF) technology to EV pretreatment protocols and demonstrate a rapid and fully automated sample preparation platform for clinical tumor liquid biopsy. Combining a reusable DMF chip technique with a low-cost EV isolation and miRNA preparation protocol, the platform completes automated sample processing in 20-30 min, supporting immediate RT-qPCR analyses on EV-derived miRNAs (EV-miRNAs). The utility and reliability of the platform was validated via clinical sample processing for EV-miRNA detection. With 23 tumor and 20 non-tumor clinical plasma samples, we concluded that EV-miR-486-5p and miR-21-5p are effective biomarkers for NSCLC with a small sample volumn (20-40 µL). The result was consistent to that of a commercial exosome miRNA extraction kit. These results demonstrate the effectiveness of DMF in EV pretreatment for miRNA detection, providing a facile solution to EV isolation for liquid biopsy.

MOnitoring human papillomavirus Vaccine effect on Infection and cErvical diseases (MOVIE): Protocol for a cohort study using electronic health records from Yinzhou, China.

Cervical cancer is the fourth most common cancer in women, with a high disease burden worldwide. Human papillomavirus (HPV) vaccination reduces HPV-related infection and associated cervical lesions and cancers. Few studies have explored HPV vaccination impact in real-world settings in China. This study aims to monitor HPV vaccine uptake and its effects on HPV-related diseases, evaluating vaccine effectiveness in a real-world context and complementing clinical trial results. Electronic health records (EHRs) from 2010 to 2020 from the Yinzhou Regional Health Information Platform (YRHIP) will be queried/extracted to identify and monitor HPV vaccine uptake in females aged 9-45 years, and HPV-related screening and prevalence (i.e., cervical HPV infection, cervical intraepithelial neoplasia [CIN] grades 1-3, and cervical cancer) in a cohort of females aged 9-70 years. Cervical cancer screening guidelines and expert consultation will be used for intra-database validation, to determine the best algorithm for identifying HPV-related disease. Pre-launch (2010-2016) and post-launch (2018-2020) periods are predefined. A time trend analysis will be performed to describe the vaccination impact on disease prevalence and, if prerequisite conditions are met, vaccine effectiveness will be computed using logistic regression, adjusting for age, calendar year, history of screening and HPV infection. Cohort study design, outcomes validation, data linkage, and multi-step statistical analyses could provide valuable experience for designing other real-world studies in the future. The study outcomes can help inform policy-makers about uptake and HPV vaccination policy in girls and women in Yinzhou District, and provide insights on progress toward achieving goals set by the World Health Organization.

Construction land suitability assessment in rapid urbanizing cities for promoting the implementation of United Nations sustainable development goals: a case study of Nanchang, China.

Cities, the main place of human settlements, are required to offer high-quality environments to citizens. To achieve this, it is essential to overcome several mega challenges of urbanization, population growth, economic development, environmental deterioration, and climate change. Urban infrastructure construction is capable of enhancing economic growth and promoting urban sustainability, while it will lead to many environmental problems if the infrastructure construction is not properly planned and designed. To address this challenge, this study aims to understand how to ensure the construction land expansion sustainably in rapidly urbanizing cities. In particular, this study analyzed the suitability of construction land expansion in Nanchang, a rapid urbanizing city in China, from 1995 to 2015. The results indicate that the urban expansion speed from 1995 to 2005 was faster than that from 2005 to 2015. The construction land in Nanchang was expanding towards "all directions" and sprawled towards surrounding districts and counties from the original core areas. Nevertheless, about 70% of the Nanchang area was allowable construction area (highly suitable expansion, relatively suitable expansion, and basically suitable expansion areas), indicating that the abundant reserved land resources for urban construction. This study also identified multiple suitability expansion paths of construction land, providing a scientific guidance for the land use planning of Nanchang city. Overall, this study provides a reference to the understanding of the construction land expansion for the achievement of United Nations sustainable development goals. It can also promote the understanding of spatial territory planning and practically enhance the capabilities of land use planning and design.

A systematic literature review to assess the burden of herpes zoster disease in China.

INTRODUCTION: Herpes zoster (HZ) or shingles occurs as a result of reactivation after a primary infection with varicella zoster virus (chickenpox). The burden of HZ in older adults in China is not well understood. We conducted a systematic literature review to understand the burden of disease related to HZ, its complications, and associated costs in China. AREAS COVERED: Using publications retrieved from Chinese and English literature databases, we described incidence and prevalence of HZ, occurrence of HZ-related complications, and costs associated with HZ in mainland China, Taiwan, and Hong Kong. EXPERT OPINION: The data, although limited, indicate that the burden of disease due to HZ is substantial in China, with incidence rates that are comparable to the rest of the world. Recently, an adjuvanted recombinant HZ vaccine was approved for use in China. Disease prevention is likely to reduce the burden of disease, with potentially significant economic benefits. However, understanding the public health impact of vaccination in China will require extensive baseline information about incidence, complication rates, and associated costs. This review gives an overview of available research, but also reveals existing gaps. Well-designed observational studies are needed to quantify the total burden of disease and potential impact of prevention through vaccination.

PLAIN LANGUAGE SUMMARY What is the context? Although Herpes zoster (shingles) is a common disease of older age, the burden of disease in China is not well described. 32% of the Chinese population is aged 50 years and Older and this proportion is increasing. As a result of the ageing population, the public burden associated with shingles is expected to increase over time. What is new? We accessed published studies in the English and Chinese language literature to explore available information describing shingles in China. The incidence of shingles in Taiwan, Hong Kong and mainland China appears to be similar to other countries, although reliable population-based data are currently sparse in Hong Kong and mainland China. What is the impact? Data describing the disease burden due to shingles are currently heterogeneous throughout China. This review is a first step to determine those populations which could benefit most from shingles vaccination. Preventing shingles through vaccination could benefit the individual as well as provide potentially significant economic benefits for the individual, the employer and the economy.

A POI and LST Adjusted NTL Urban Index for Urban Built-Up Area Extraction.

Nighttime light (NTL) images have been broadly applied to extract urban built-up areas in recent years. However, the typical NTL images provided by Defense Meteorological Satellite Program/Operational Linescan System (DMSP/OLS) and National Polar-Orbiting Partnership's Visible Infrared Imaging Radiometer Suite (NPP/VIIRS) have the drawbacks of low resolution and blooming effect, which bring difficulty for the application of them in urban built-up area extraction. Therefore, this paper proposes the POI (point of interest) and LST (land surface temperature) adjusted NTL urban index (PLANUI) to extract the urban built-up areas with high accuracy. PLANUI is the first urban index to integrate POI and NTL for urban built-up area extraction. In this paper, NPP/VIIRS and Luojia 1-01 images were introduced as the original NTL data and the vegetation adjusted NTL urban index (VANUI) was selected as the comparison item. The threshold method was utilized to extract urban built-up areas from these data. The results show that: (1) Based on the comparison with the reference data, the PLANUI can make up the shortcoming of low resolution and the blooming effect of NTL effectively. (2) Compared with the VANUI, the PLANUI can significantly improve the accuracy of the urban built-up areas extracted and characterize urban features. (3) According to the results based on NPP/VIIRS and Luojia 1-01 images, the PLANUI has extensive applicability, both for regions with different degrees of economic development and NTL data with different resolutions. PLANUI can enhance the features of urban built-up areas with social sensing data and natural remote sensing data, which helps to weaken the NTL blooming effect and improve the extraction accuracy. PLANUI can provide an effective approach for urban built-up area extraction, which plays a certain guiding role for the study of urban structure, urban expansion, and urban planning and governance.

Assessment of Landscape Ecological Health: A CaseStudy of a Mining City in a Semi-Arid Steppe.

The ecological status of the semi-arid steppes in China is fragile. Under the long-term and high-intensity development of mining, the ecological integrity and biodiversity of steppe landscapes have been destroyed, causing soil pollution, grassland degradation, landscape function defect, and so on. Previous studies have mainly focused on ecosystem health assessment in mining areas. Landscape ecological health (LEH) pays more attention to the interactions between different ecosystems. Therefore, the ecological assessment of mining cities is more suitable on a landscape scale. Meanwhile, the existing LEH assessment index systems are not applicable in ecologically fragile areas with sparse population, underdeveloped economy, and in relatively small research areas. The purpose of this study was to construct a LEH assessment index system and evaluate the LEH of a mining city located in a semi-arid steppe. Xilinhot is a typical semi-arid steppe mining city in China. The contradictions between the human, land and ecological environment are serious. A new model Condition, Vigor, Organization, Resilience, and Ecosystem (CVORE) model was constructed that integrated five subsystems (services) from the perspectives of ecology, landscape ecology, mining science, and geography. This study used the CVORE model to systematically evaluate the LEH in Xilinhot city in terms of five LEH levels, including very healthy, healthy, sub-healthy, unhealthy and morbid landscape. Research results show that the areas of the very healthy, healthy, sub-healthy, unhealthy and morbid landscapes are 13.23, 736.35, 184.5, 66.76 and 20.63 km², respectively. The healthy landscapes area accounts for 72.08% and most grasslands are healthy. The sub-healthy landscapes are mainly located around areas with higher disturbances due to human activities. The morbid or unhealthy landscapes are concentrated in the mining areas. The proposed CVORE model can enrich the foundations for the quantitative assessment of Landscape Ecological Health of Mining Cities in Semi-arid Steppe (LEHMCSS). This study provided a new LEH assessment approach (CVORE model), which can support landscape ecological restoration, ecological environmental protection and urban planning of the semi-arid steppe mining cities.

Quantitative assessment of gene promoter methylation in non-small cell lung cancer using methylation-sensitive high-resolution melting.

DNA methylation is closely associated with aberrant epigenetic changes. Previous studies have identified various genes associated with non-small cell lung cancer (NSCLC), but the precise combination responsible for its etiology is still debated. The aim of the present study was to select a new set of NSCLC-related genes using methylation-sensitive high-resolution melting. The promoter methylation status of six selected genes, consisting of protocadherin γ subfamily B, 6 (PCDHGB6), homeobox A9 (HOXA9), O6-methylguanine-DNA methyltransferase (MGMT), microRNA (miR)-126, suppressor of cytokine signaling 3 (SOCS3) and Ras association domain family member 5, also termed NORE1A, was evaluated in 54 NSCLC patients. From these samples, genome-wide DNA was extracted and bisulfite conversion was performed along with fluorogenic quantitative polymerase chain reaction to detect methylation values of the six selected promoters. The present results revealed frequent methylation on PCDHGB6, HOXA9 and miR-126, which contrasted with infrequent methylation on MGMT. The results indicated no methylation on either SOCS3 or NORE1A. The sensitivity and specificity of the methylation assessment were 85.2 and 81.5%, respectively, and the analysis results were validated by pyrosequencing. Furthermore, minute comparison of the association between DNA methylation and clinical features was performed. Overall, these results may provide potential information for the development of better clinical diagnostics and more targeted and effective therapies for NSCLC.

An economic analysis of adult hepatitis B vaccination in China.

BACKGROUND AND OBJECTIVE: With the universal infant hepatitis B vaccination (HepB) program, China has made remarkable achievements to prevent and control hepatitis B. In order to further reduce hepatitis B virus (HBV) infection, the Chinese government is considering implementing a widespread adult HBV vaccination campaign. We performed an economic analysis of two different adult HepB vaccination strategies for 21-59-years-olds: vaccination without screening and screening-based vaccination. METHODS: Cost-benefit analyses were conducted. All 21-59-year-olds were divided into two groups: young adults (ages 21-39) and middle-aged adults (ages 40-59). Costs and benefits were estimated using the direct cost and societal (direct and indirect costs) perspectives. All costs and benefits were adjusted to 2014 US dollars, where future values were discounted at a 3% annual rate. We calculated benefit-cost ratios (BCRs) of the two vaccination strategies for the two different age groups. Sensitivity analyses varied key parameters within plausible ranges. RESULTS: Among young adults, the direct and societal BCRs for a vaccination campaign with no screening would be 1.06 and 1.42; with a screening-based vaccination campaign, the model estimated the direct and societal BCRs would be 1.19 and 1.73. Among middle-aged adults, the direct and societal BCRs for a vaccination campaign without screening would be 0.59 and 0.59; with a screening-based vaccination campaign, the model estimated the direct and societal BCRs would be 0.68 and 0.73. CONCLUSION: The results of our study support a HepB vaccination campaign for young adults. Additionally, a vaccination campaign with screening appeared to provide greater value than a vaccination without screening.

Quantitative assessment of Aß peptide in brain, cerebrospinal fluid and plasma following oral administration of γ-secretase inhibitor MRK-560 in rats.

The ß-amyloid peptides (Aß) are thought to play a critical role in the pathophysiology of Alzheimer's disease. One therapeutic strategy aimed to reduce or eliminate the production of Aß peptides is inhibition of the γ-secretase enzyme, which cleaves amyloid precursor protein to form Aß peptides. We studied the in vivo effects of the potent, orally bioavailable and brain penetrant γ-secretase inhibitor (GSI), MRK-560, on both Aßx-40 and Aßx-42 in multiple compartments (plasma, the brain and cerebrospinal fluid) of rat. Although there were differences in the time course and magnitude of the changes, the results showed that MRK-560 caused marked inhibition of both Aßx-40 and Aßx-42 in all three compartments. We identified good correlations between plasma Aßx-40 versus brain Aßx-40 (r = 0.84), and plasma Aßx-40 versus CSF Aßx-40 (r = 0.85), indicating that these pools of Aß are related dynamically. These results suggest that central Aß changes that occur following acute dosing with MRK-560 can be predicted based on plasma Aß changes and could thus serve as a useful biomarker to help accelerate decision-making during early clinical development.

Cost-effectiveness analysis of a hepatitis B vaccination catch-up program among children in Shandong Province, China.

OBJECTIVE: The aim of the study was to estimate long-term cost­effectiveness of a hepatitis B vaccination catch-up program among children born between 1994 and 2001 (when they were 8­15 y old) in Shandong province, China, to provide information for nationwide evaluation and future policy making. METHODS: We determined the cost-effectiveness of the catch-up program compared with the status quo (no catch-up program). We combined a Decision Tree model and a Markov model to simulate vaccination and clinical progression after hepatitis B virus (HBV) infection. Parameters in the models were from the literature, a field survey, program files, and the National Notifiable Disease Reporting System (NNDRS). The incremental cost­effectiveness ratio (ICER) was used to compare the 2 alternative strategies. One-way sensitivity analysis, 2-way sensitivity analysis, and probability sensitivity analysis were used to assess parameter uncertainties. RESULTS: The catch-up program was dominant compared with the status quo. Using a total of 5.53 million doses of vaccines, the catch-up program could prevent 21,865 cases of symptomatic acute hepatitis B, 3,088 carrier states with positive hepatitis B surface antigen (HBsAg), and 812 deaths due to HBV infection. The catch-up program could add 28,888 quality-adjusted life years (QALYs) and save $192.01 million in the targeted population in the future. The models were robust, considering parameter uncertainties. CONCLUSION: The catch-up program in Shandong province among children born between 1994 and 2001 was 'very cost-saving.' It could save life years and reduce total future costs. Our study supported the desirability and impact of such a catch-up program throughout China.

Preventing hepatitis B though universal vaccination: reduction of inequalities through the GAVI China project.

OBJECTIVE: In order to measure hepatitis B coverage and progress in equality with respect to protection against hepatitis B in poverty-affected areas funded by the Global Alliance on Vaccine and Immunization project funded in poverty-affected counties. METHODS: We reviewed routinely reported coverage data and conducted a national stratified, validation, cross-sectional survey in October 2010, according to WHO recommended sampling method. First, we stratified China into three regions (Eastern, Central and Western) based on economic criteria. Second, in each region, we selected eight counties with a probability proportional to population size. Third, in each selected county, we selected (a) 10 townships at random among the list of townships of the county. RESULTS: We visited 244 townships as part of the final evaluation (71 in the East, 86 in the Center and 87 in the West). Overall, in these 244 townships, surveyed TBD coverage increased from 60% in 2002 to 91% in 2009 and surveyed three dose of hepatitis B vaccine coverage increased from 71% in 2002 to 93% in 2009. Overall, in the GAVI supported areas, the HepB3/DTP3 ratio increased from 57% in 2002 to 94% in 2009. CONCLUSION: Pro-poor GAVI approach was an effective way to reduce inequity among children through provision of free vaccination. When vaccine and AD syringes were provided for free, they closed the gap between Eastern and Western regions and between the rich and the poor.