The assessment of circulating tumor DNA associated with Wnt/ß-catenin signaling pathway as a diagnostic tool for liver cancer: a systematic review and meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) in peripheral blood has become a promising noninvasive biomarker. However, the diagnostic potential of Wnt/ß-catenin signaling pathway-related ctDNA for liver cancer is controversial. Here, we aimed to access the diagnostic potential and clinicopathological features of Wnt/ß-catenin signaling pathway-related ctDNA in liver cancer and provide data support for its clinical diagnosis and treatment. METHODS: A comprehensive literature search was conducted to identify the relevant studies. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. The bivariate linear mixed models were used. RESULTS: The AUC (area under the curve), pooled sensitivity and specificity were 0.77, 0.42 and 0.98, respectively. The findings suggested that control type, sample source, research methods and thresholds were the potential sources of heterogeneity (p < 0.05). Additionally, this study also found that there were significant correlations between the hypermethylation of Wnt/ß-catenin signaling pathway-related ctDNA and tumor size, TNM stage, distant metastasis, and HBV infection(p < 0.05). CONCLUSION: This study confirmed that Wnt/ß-catenin signaling pathway-related ctDNA had the better diagnostic potential for liver cancer and might be an effective complementary tool for serum AFP assays in the early diagnosis of liver cancer. PROSPERO: (No. CRD42023404984).[Figure: see text].

Causality Assessment Between Idiopathic Inflammatory Myopathies and Lung Cancer: A Bidirectional 2-Sample Mendelian Randomization.

BACKGROUND: Although observational studies have revealed associations between idiopathic inflammatory myopathies (IIMs) and lung cancer (LC), they have not established a causal relationship between these 2 conditions. METHODS: We used a 2-sample Mendelian randomization approach to examine the bidirectional causal associations between IIMs and LC, using single-nucleotide polymorphisms selected from high-quality genome-wide association studies in the FinnGen database. Sensitivity analyses were conducted to assess potential heterogeneity and pleiotropy impacts on the Mendelian randomization results. RESULTS: Our analysis demonstrated a positive causal effect of genetically increased IIM risk on LC (odds ratio, 1.114; 95% confidence interval, 1.057-1.173; p = 5.63 × 10-5), particularly on the lung squamous cell carcinoma subtype (odds ratio, 1.168, 95% confidence interval, 1.049-1.300, p = 0.00451), but not on lung adenocarcinoma or small cell lung cancer. No causal effect of LC on IIMs was identified. Sensitivity analyses indicated that horizontal pleiotropy was unlikely to influence causality, and leave-one-out analysis confirmed that the observed associations were not driven by a single-nucleotide polymorphism. CONCLUSION: Our findings offer compelling evidence of a positive causal relationship between IIMs and LC, particularly with regard to lung squamous cell carcinoma, in the European population. Conversely, there is no evidence of LC causing IIMs. We recommend that LC diagnosis consider the specific characteristics of IIMs.

Emergency department visits by older adults receiving postacute care in skilled nursing facilities.

Skilled nursing facilities (SNF) represent a common postdischarge destination for hospitalized older adults. The goals of SNF care include the completion of extended skilled nursing care and physical rehabilitation to enable patients to safely return home. However, nearly one in four older adults discharged to SNF are rehospitalized and one in five seek care in the emergency department (ED) but are discharged back to SNF. Our aim was to measure the national prevalence and costs to Medicare of ED visits by SNF patients. Of the 1,551,703 Medicare beneficiaries discharged to SNF in 2019, 16.3% had an ED visit within 14 days (n = 253,104). Of those ED visits, 25.5% resulted in a same-day discharge back to SNF (n = 64,472), costing Medicare $24.6 million. Novel care models that can leverage SNF staff and resources while providing rapid diagnostic services are urgently needed.

Efficiency trends of essential public health services and possible influencing factors since the new round health reform in China: a case study from Hainan Province.

Objective: This article aimed to evaluate the efficiency trends and influencing factors of essential public health services in Hainan Province after the healthcare reform launched in 2009 in China. Methods: The efficiency of essential public health services (EPHS) at primary health institutions was assessed using data envelopment analysis (DEA), and the efficiency change was analyzed by employing the Malmquist productivity index (MPI). We used Tobit regression to identify the influence of environmental factors on the efficiency of public health services. The bootstrap method was adopted to reduce the impact of random errors on the result. Results: The bootstrapping bias-corrected efficiency revealed that the average values of technical efficiency, pure technical efficiency, and scale efficiency were 0.7582, 0.8439, and 0.8997, respectively, which meant that the EPHS in Hainan Province were not at the most effective state. The average bias-corrected MPI was 1.0407 between 2010 and 2011 and 1.7404 between 2011 and 2012. MPIs were less than 1.0000 during other periods investigated, ranging from 0.8948 to 0.9714, indicating that the efficiency of EPHS has been decreasing since 2013. The Tobit regression showed that the regression coefficients of per capita GDP, population density, the proportion of older people aged over 65, and the proportion of ethnic minority population were 0.0286, -0.0003, -0.0316, and - 0.0041 respectively, which were statistically significant (p < 0.05). Conclusion: There was a short-term improvement in the efficiency of EPHS in Hainan after the launch of the new round of health reform. However, this trend has not been sustained after 2013. In particular, equalized financial investment in essential public health could not fulfill the needs of poor counties. This has resulted in the inability to improve scale efficiency in some counties, which in turn has affected the improvement of overall EPHS efficiency. Therefore, to promote EPHS efficiency sustainably, it is suggested that under this model of provincial control of counties, the equity of resource allocation should be effectively improved while further advancing the technology of service delivery.

Cardiovascular Disease Burden and Outcomes Among American Indian and Alaska Native Medicare Beneficiaries.

Importance: American Indian and Alaska Native persons face significant health disparities; however, data regarding the burden of cardiovascular disease in the current era is limited. Objective: To determine the incidence and prevalence of cardiovascular disease, the burden of comorbid conditions, including cardiovascular disease risk factors, and associated mortality among American Indian and Alaska Native patients with Medicare insurance. Design, Setting, and Participants: This was a population-based cohort study conducted from January 2015 to December 2019 using Medicare administrative data. Participants included American Indian and Alaska Native Medicare beneficiaries 65 years and older enrolled in both Medicare part A and B fee-for-service Medicare. Statistical analyses were performed from November 2022 to April 2023. Main Outcomes and Measures: The annual incidence, prevalence, and mortality associated with coronary artery disease (CAD), heart failure (HF), atrial fibrillation/flutter (AF), and cerebrovascular disease (stroke or transient ischemic attack [TIA]). Results: Among 220 598 American Indian and Alaska Native Medicare beneficiaries, the median (IQR) age was 72.5 (68.5-79.0) years, 127 402 were female (57.8%), 78 438 (38.8%) came from communities in the most economically distressed quintile in the Distressed Communities Index. In the cohort, 44.8% of patients (98 833) were diagnosed with diabetes, 61.3% (135 124) were diagnosed with hyperlipidemia, and 72.2% (159 365) were diagnosed with hypertension during the study period. The prevalence of CAD was 38.6% (61 125 patients) in 2015 and 36.7% (68 130 patients) in 2019 (P < .001). The incidence of acute myocardial infarction increased from 6.9 per 1000 person-years in 2015 to 7.7 per 1000 patient-years in 2019 (percentage change, 4.79%; P < .001). The prevalence of HF was 22.9% (36 288 patients) in 2015 and 21.4% (39 857 patients) in 2019 (P < .001). The incidence of HF increased from 26.1 per 1000 person-years in 2015 to 27.0 per 1000 person-years in 2019 (percentage change, 4.08%; P < .001). AF had a stable prevalence of 9% during the study period (2015: 9.4% [14 899 patients] vs 2019: 9.3% [25 175 patients]). The incidence of stroke or TIA decreased slightly throughout the study period (12.7 per 1000 person-years in 2015 and 12.1 per 1000 person-years in 2019; percentage change, 5.08; P = .004). Fifty percent of patients (110 244) had at least 1 severe cardiovascular condition (CAD, HF, AF, or cerebrovascular disease), and the overall mortality rate for the cohort was 19.8% (43 589 patients). Conclusions and Relevance: In this large cohort study of American Indian and Alaska Native patients with Medicare insurance in the US, results suggest a significant burden of cardiovascular disease and cardiometabolic risk factors. These results highlight the critical need for future efforts to prioritize the cardiovascular health of this population.

Quantitative assessment of lipophilic membrane dye-based labelling of extracellular vesicles by nano-flow cytometry.

Although lipophilic membrane dyes (LMDs) or probes (LMPs) are widely used to label extracellular vesicles (EVs) for detection and purification, their labelling performance has not been systematically characterized. Through concurrent side scattering and fluorescence detection of single EVs as small as 40 nm in diameter by a laboratory-built nano-flow cytometer (nFCM), present study identified that (1) PKH67 and PKH26 could maximally label ∼60%-80% of EVs isolated from the conditioned cell culture medium (purity of ∼88%) and ∼40%-70% of PFP-EVs (purity of ∼73%); (2) excessive PKH26 could cause damage to the EV structure; (3) di-8-ANEPPS and high concentration of DiI could achieve efficient and uniform labelling of EVs with nearly 100% labelling efficiency for di-8-ANEPPS and 70%-100% for DiI; (4) all the four tested LMDs can aggregate and form micelles that exhibit comparable side scatter and fluorescence intensity with those of labelled EVs and thus hardly be differentiate from each other; (5) as the LMD concentration went up, the particle number of self-aggregates increased while the fluorescence intensity of aggregates remained constant; (6) PKH67 and PKH26 tend to form more aggregated micelles than di-8-ANEPPS and DiI, and the effect of LMD self-aggregation can be negligible at optimal staining conditions. (7) All the four tested LMDs can label almost all the very-low-density lipoprotein (VLDL) particles, indicating potential confounding factor in plasma-EV labelling. Besides, it was discovered that DSPE-PEG2000 -biotin can only label ∼50% of plasma-EVs. The number of LMP inserted into the membrane of single EVs was measured for the first time and it was confirmed that membrane labelling by lipophilic dyes did not interfere with the immunophenotyping of EVs. nFCM provides a unique perspective for a better understanding of EV labelling by LMD/LMP.

Improvement Pathways for Urban Land Use Efficiency in the Beijing-Tianjin-Hebei Urban Agglomeration at the County Level: A Context-Dependent DEA Based on the Closest Target.

One of the most effective ways to achieve sustainable land use and the regional coordinated development of urban agglomerations lies in improving the urban land use efficiency (ULUE) of both large, medium, and small cities and small towns. However, in previous studies, less attention has been paid to pathways for potential improvement, especially at the county level. The main purpose of this paper is to examine potential improvement paths for the ULUE at the county level in urban agglomerations, while attempting to provide more practical targets for improvement and formulate more reasonable improvement steps for inefficient counties. Therefore, a total of 197 counties in the Beijing-Tianjin-Hebei urban agglomeration (BTHUA) in 2018 were taken as examples to build a context-dependent data envelopment analysis (DEA) model based on the closest target. In addition, by utilizing methods such as the significant difference test and system clustering analysis, the shortest path and steps to achieve efficiency were identified for inefficient counties, and the characteristics of improvement paths at different levels were summarized. Furthermore, improvement pathways were compared for two dimensions: administrative type and region. The results showed that the causes of polarization for ULUE at different levels were mainly reflected in more complex targets to be improved in the middle- and low-level counties than at high levels. Improving environmental and social benefits was essential to achieving efficiency in most inefficient counties, especially at the middle and low levels. The improvement paths for inefficient counties between different administrative types, as well as the prefecture-level cities, were heterogeneous. The results of this study can provide a policy and planning basis for improving urban land use. This study is of practical significance in accelerating the development of urbanization and the promotion of regional coordination and sustainable development.

Vehicle emissions of primary air pollutants from 2009 to 2019 and projection for the 14th Five-Year Plan period in Beijing, China.

Over the past decade, the emission standards and fuel standards in Beijing have been upgraded twice, and the vehicle structure has been improved by accelerating the elimination of 2.95 million old vehicles. Through the formulation and implementation of these policies, the emissions of carbon monoxide (CO), volatile organic compounds (VOCs), nitrogen oxides (NOx), and fine particulate matter (PM2.5) in 2019 were 147.9, 25.3, 43.4, and 0.91 kton in Beijing, respectively. The emission factor method was adopted to better understand the emissions characteristics of primary air pollutants from combustion engine vehicles and to improve pollution control. In combination with the air quality improvement goals and the status of social and economic development during the 14th Five-Year Plan period in Beijing, different vehicle pollution control scenarios were established, and emissions reductions were projected. The results show that the emissions of four air pollutants (CO, VOCs, NOx, and PM2.5) from vehicles in Beijing decreased by an average of 68% in 2019, compared to their levels in 2009. The contribution of NOx emissions from diesel vehicles increased from 35% in 2009 to 56% in 2019, which indicated that clean and energy-saving diesel vehicle fleets should be further improved. Electric vehicle adoption could be an important measure to reduce pollutant emissions. With the further upgrading of vehicle structure and the adoption of electric vehicles, it is expected that the total emissions of the four vehicle pollutants can be reduced by 20%-41% by the end of the 14th Five-Year Plan period.

Legacy of agrochemicals in the circular food economy: Glyphosate-based herbicides introduced via manure fertilizer affect the yield and biochemistry of perennial crop plants during the following year.

Conventional agricultural practices favoring the use of glyphosate-based herbicides (GBHs) increase the risk of GBH residues ending up in animal feed, feces, and, eventually, manure. The use of poultry manure as organic fertilizer in the circular food economy increases the unintentional introduction of GBH residues into horticultural and agricultural systems, with reportedly negative effects on the growth and reproduction of crop plants. To understand the potential lasting effects of exposure to GBH residues via organic manure fertilizers, we studied strawberry (Fragaria x vescana) plant performance, yield quantity, biochemistry, folivory, phytochemistry, and soil elemental composition the year after exposure to GBH. Although plants exposed to GBH residues via manure fertilizer were, on average, 23% smaller in the year of exposure, they were able to compensate for their growth during the following growing season. Interestingly, GBH residue exposure in the previous growing season led to a trend in altered plant size preferences of folivores during the following growing season. Furthermore, the plants that had been exposed to GBH residues in the previous growing season produced 20% heavier fruits with an altered composition of phenolic compounds compared to non-exposed plants. Our results indicate that GBHs introduced via manure fertilizer following circular economy practices in one year can have effects on perennial crop plants in the following year, although GBH residues in soil have largely vanished.

Research on Ecological Effect Assessment Method of Ecological Restoration of Open-Pit Coal Mines in Alpine Regions.

Open-pit mining is an important form of coal mining in China, and its damage to the ecological environment is particularly obvious in alpine regions. The ecological restoration of alpine open-pit coal mines faces severe challenges, and its restoration effect will directly affect the ecological security of China. Meanwhile, comprehensive and system-oriented evaluation of ecological restoration effects is still insufficient in current research. In this study, we selected different quantities of assessment factors on the two scales of ecological project area and ecological impact area to evaluate the ecological restoration effect of an alpine open-pit coal mine. Then, we formed a multi-scale and multi-dimensional ecological restoration effect assessment model of the alpine open-pit coal mine and used this model to analyze the implementation effect of the ecological restoration project of the Baiyinhua No. 2 Open-pit Mine. The results show that the multi-scale and multi-dimensional ecological restoration effect assessment model of alpine open-pit coal mine proposed in this study can accurately characterize the restoration effect of open-pit coal mines in alpine regions and can also be used as a significant evaluation tool in the future ecological construction of mining areas. This study hopes the multi-scale and multi-dimensional ecological restoration effect assessment model of alpine open-pit coal mine can provide a comprehensive, systematic, and scientific evaluation method for the ecological restoration of alpine open-pit coal mines and provide a scientific basis for the ecological restoration and green development of relevant mining areas.

Spatial analysis, coupling coordination, and efficiency evaluation of green innovation: A case study of the Yangtze River Economic Belt.

Green innovation is an important driving force to promote the sustainable development of urban society and economy. This paper constructs an evaluation index system containing social undesirable outputs, and uses the Super-SBM model and the Malmquist-Luenberger index to evaluate green innovation efficiency in 42 cities along the Yangtze River Economic Belt from 2013 to 2017. Additionally, spatial autocorrelation analysis is used to study the spatial correlation of green innovation efficiency. Finally, the coupling coordination degree model is used to study the coupling coordination degree between green innovation efficiency and high-tech industries. The following results were obtained. (1) The average value of green innovation efficiency increased from 1.0446 to 1.0987, and the annual average growth rate of total factor productivity of green innovation was 1.1%. (2) Green innovation efficiency of the Yangtze River Economic Belt had a significant spatial positive correlation, but the types of agglomeration among cities in different sections of the Yangtze River were quite different. (3) The coupling coordination degree between green innovation efficiency and the development level of high-tech industries in the cities of the Yangtze River Economic Belt was in the basic coordination stage. Based on the research results, we suggest that cities in this belt further enhance the interactive relationship between green innovation and economic development and promote the coordinated development of economy and society.

Psychometric properties of the Chinese version of the Attitudes Toward Accompanied Driving Scale and its relationship with driving styles.

The present study aimed to adapt the Attitudes Toward Accompanied Driving Scale (ATADS) to a Chinese drivers sample and to examine its reliability and validity. Five hundred and seventy-two drivers aged 18 to 25 years old were asked to complete the ATADS and a validated Chinese version of the Multidimensional Driving Style Inventory. The factorial structure of the ATADS was examined using exploratory factor analysis (N = 259) and confirmatory factor analysis (N = 313). The validity of the scale was evaluated by examining the associations between the ATADS factors, demographic variables and driving styles. The results showed that both the findings of the EFA and CFA showed a five-factor structure of the ATADS, including tension, relatedness, avoidance, disapproval and anxiety. Second, significant gender differences were found in tension, relatedness, avoidance and anxiety. Third, tension, avoidance, disapproval and anxiety were moderately or weakly correlated with risky, anxious, angry and careful driving styles. Moreover, the number of traffic accidents after the accompanying phase was positively correlated with disapproval and avoidance. The findings supported the psychometric properties of the Chinese version of the ATADS and highlighted the adverse effects of young drivers' negative attitudes toward accompanied driving on their driving styles.

Incidence and outcomes of acute respiratory distress syndrome in intensive care units of mainland China: a multicentre prospective longitudinal study.

OBJECTIVES: To evaluate the incidence and mortality of acute respiratory distress syndrome (ARDS) in medical/respiratory intensive care units (MICUs/RICUs) to assess ventilation management and the use of adjunct therapy in routine clinical practice for patients fulfilling the Berlin definition of ARDS in mainland China. METHODS: This was a multicentre prospective longitudinal study. Patients who met the Berlin definition of ARDS were included. Baseline data and data on ventilator management and the use of adjunct therapy were collected. RESULTS: Of the 18,793 patients admitted to participating ICUs during the study timeframe, 672 patients fulfilled the Berlin ARDS criteria and 527 patients were included in the analysis. The most common predisposing factor for ARDS in 402 (77.0) patients was pneumonia. The prevalence rates were 9.7% (51/527) for mild ARDS, 47.4% (250/527) for moderate ARDS, and 42.9% (226/527) for severe ARDS. In total, 400 (75.9%) patients were managed with invasive mechanical ventilation during their ICU stays. All ARDS patients received a tidal volume of 6.8 (5.8-7.9) mL/kg of their predicted body weight and a positive end-expository pressure (PEEP) of 8 (6-12) cmH2O. Recruitment manoeuvres (RMs) and prone positioning were used in 61 (15.3%) and 85 (16.1%) ventilated patients, respectively. Life-sustaining care was withdrawn from 92 (17.5%) patients. When these patients were included in the mortality analysis, 244 (46.3%) ARDS patients (16 (31.4%) with mild ARDS, 101 (40.4%) with moderate ARDS, and 127 (56.2%) with severe ARDS) died in the hospital. CONCLUSIONS: Among the 18 ICUs in mainland China, the incidence of ARDS was low. The rates of mortality and withdrawal of life-sustaining care were high. The recommended lung protective strategy was followed with a high degree of compliance, but the implementation of adjunct treatment was lacking. These findings indicate the potential for improvement in the management of patients with ARDS in China. TRIAL REGISTRATION: Clinicaltrials.gov NCT02975908 . Registered on 29 November 2016-retrospectively registered.

Impact of atherosclerotic cardiovascular disease on healthcare resource utilization and costs in patients with type 2 diabetes mellitus in a real-world setting.

BACKGROUND: This study evaluated the impact of atherosclerotic cardiovascular disease (ASCVD) on healthcare resource utilization and costs in patients with type 2 diabetes mellitus (T2DM). METHODS: This study was a retrospective, cross-sectional study using US claims data. Adult patients with T2DM were stratified by presence or absence of ASCVD and compared regarding annual (2015) healthcare resource utilization and associated costs. Subgroup analyses were conducted for three age groups (18-44, 45-64, and ≥ 65 years). RESULTS: Among 1,202,596 eligible patients with T2DM, 45.2% had documented ASCVD. The proportions of patients with inpatient and ER-based resource utilization during 2015 were three-to-four times greater in the ASCVD cohort as compared to the non-ASCVD cohort for the categories of inpatient visits (15.6% vs 4.4% of patients), outpatient ER visits (18.4% vs 5.2% of patients), and inpatient ER visits (4.3% vs 0.9% of patients). Outpatient utilization also was higher among patients with ASCVD as compared to those without ASCVD (mean number of annual office visits per patient, 9.1 vs 5.6), and more than twice as many patients with ASCVD had ≥ 9 office visits (43.5% vs 19.8%). Average per-patient total healthcare cost was $22,977 for ASCVD vs $9735 for non-ASCVD, with medical costs primarily driving the difference ($17,849 vs $6079); the difference in pharmacy costs was smaller ($5128 vs $3656). In the 18-44, 45-64, and ≥ 65 age subgroups respectively, total annual healthcare costs were 143, 127, and 114% higher in ASCVD vs non-ASCVD patients. CONCLUSIONS: These findings indicate significantly higher healthcare resource utilization and associated costs in patients having T2DM with ASCVD compared to T2DM without ASCVD.

Initial prospective study of ambulatory mPCNL on upper urinary tract calculi.

OBJECTIVE: To explore the feasibility and safety of ambulatory mPCNL (mini percutaneous nephrolithotomy) on upper urinary tract calculi. METHODS: Clinical data of 18 patients received ambulatory mPCNL during Aug. 2017 to Jan. 2018 and 23 patients treated with routine inpatient mPCNL of the corresponding period were collected. All the patients included received 16Fr channel PCNL under the guidance of Doppler ultrasound. A 6Fr double J stent was placed in the ureter for internal drainage, and either an indwelling 14Fr open nephrostomy tube was placed or the puncture channel was filled with absorbable hemostatic materials alone, depends on the bleeding condition of the puncture channel and the intraoperative conditions. Preoperative parameters and surgery time, complications, total hospitalization costs and hospital stay time between the two groups were compared. RESULTS: Preoperative parameters regarding age (P=0.057), sex distribution (P=0.380), ASA score (P=0.388), Calculi CT value (P=0.697), and the S.T.O.N.E. score (P=0.122) were comparable between the two groups. Maximum diameter of calculi (cm) of the conventional hospitalization group, however, was larger than the ambulatory surgery group (P=0.041). There were no significant differences in the mean surgery time (P=0.146), postoperative hemoglobin drop (P=0.865), Calculi-free rate on the next day after surgery (P=0.083) and postoperative fever rate (P=0.200) between the two groups. With regard to tubeless rate (P<0.001), total hospitalization costs (P=0.003) and hospital stay time (P<0.001), there were significant advantage favored ambulatory mPCNL. CONCLUSIONS: For patients with simple upper urinary tract calculi and relatively good performance status, ambulatory mPCNL is feasible as it's equally safe and efficient as compared with routine inpatient mPCNL. Moreover, ambulatory mPCNL decreases hospitalization costs and hospital stay time. Nevertheless, perioperative management should be carefully conducted, and well-designed studies are warranted.

Quality and efficiency assessment of six extracellular vesicle isolation methods by nano-flow cytometry.

Extracellular vesicles (EVs) have sparked tremendous interest owing to their prominent potential in diagnostics and therapeutics. Isolation of EVs from complex biological fluids with high purity is essential to the accurate analysis of EV cargo. Unfortunately, generally used isolation techniques do not offer good separation of EVs from non-EV contaminants. Hence, it is important to have a standardized method to characterise the properties of EV preparations, including size distribution, particle concentration, purity and phenotype. Employing a laboratory-built nano-flow cytometer (nFCM) that enables multiparameter analysis of single EVs as small as 40 nm, here we report a new benchmark to the quality and efficiency assessment of EVs isolated from plasma, one of the most difficult body fluids to work with. The performance of five widely used commercial isolation kits was examined and compared with the traditional differential ultracentrifugation (UC). Two to four orders of magnitude higher particle concentrations were observed for EV preparations from platelet-free plasma (PFP) by kits when compared with the EV preparation by UC, yet the purity was much lower. Meanwhile, the particle size distribution profiles of EV preparations by kits closely resembled those of PFP whereas the EV preparation by UC showed a broader size distribution at relatively large particle size. When these kits were used to isolate EVs from vesicle-depleted PFP (VD-PFP), comparable particle counts were obtained with their corresponding EV preparations from PFP, which confirmed again the isolation of a large quantity of non-vesicular contaminants. As CD9, CD63 and CD81 also exist in the plasma matrix, single-particle phenotyping of EVs offers distinct advantage in the validation of EVs compared with ensemble-averaged approaches, such as Western blot analysis. nFCM allows us to compare different isolation techniques without prejudice.

Accuracy of Tumor Perfusion Assessment in Rat C6 Gliomas Model with USPIO.

Detailed characterization of the permeability and vascular volume of brain tumor vasculature can provide essential insights into tumor physiology. In this study, we evaluated the consistency of measurements in tumor blood volume and examined the feasibility of using ultrasmall superparamagnetic iron oxide (USPIO) versus gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) as contrast agents for MR perfusion imaging of brain gliomas in C6 Rats. Eighteen rats were intracerebrally implanted with C6 glioma cells, randomly divided into two groups and examined by 3.0T perfusion MR imaging with Gd-DTPA and USPIO. Tumor relative cerebral blood volume (rCBV) and relative maximum signal reduction ratio (rSRRmax) were created based on analysis of MR perfusion images. The mean values for rCBV were 2.09 and 1.57 in the USPIO and the Gd-DTPA groups, respectively, and rSRRmax values were 1.92 and 1.02 in the USPIO and the Gd-DTPA groups, respectively, showing signifi cant differences in both rCBV and rSRRmax between the USPIO and the Gd-DTPA groups (P < 0.05). The results showed that early vascular leakage occurred with gadolinium rather than USPIO in perfusion assessment, revealing that USPIO was useful in perfusion MR imaging for the assessment of tumor vasculature.

Fruit Seeds as Sources of Bioactive Compounds: Sustainable Production of High Value-Added Ingredients from By-Products within Circular Economy.

The circular economy is an umbrella concept that applies different mechanisms aiming to minimize waste generation, thus decoupling economic growth from natural resources. Each year, an estimated one-third of all food produced is wasted; this is equivalent to 1.3 billion tons of food, which is worth around US$1 trillion or even $2.6 trillion when social and economic costs are included. In the fruit and vegetable sector, 45% of the total produced amount is lost in the production (post-harvest, processing, and distribution) and consumption chains. Therefore, it is necessary to find new technological and environmentally friendly solutions to utilize fruit wastes as new raw materials to develop and scale up the production of high value-added products and ingredients. Considering that the production and consumption of fruits has increased in the last years and following the need to find the sustainable use of different fruit side streams, this work aimed to describe the chemical composition and bioactivity of different fruit seeds consumed worldwide. A comprehensive focus is given on the extraction techniques of water-soluble and lipophilic compounds and in vitro/in vivo functionalities, and the link between chemical composition and observed activity is holistically explained.

Interrupted time-series analysis of the impact of generic market entry of antineoplastic products in China.

OBJECTIVES: The rapid growth of pharmaceutical costs is a major healthcare issue all over the world. The high prices of new drugs, especially those for cancer, are also a concern for stakeholders. Generic drugs are a major price-reducing opportunity and provide more societal value. The aim of this research is to analyse the impact of generic entry on the volume and cost of antineoplastic agents in China. METHODS: An interrupted time-series design examined monthly sales of three antineoplastic drugs (capecitabine, decitabine, imatinib) from 699 public hospitals during January 2011 to June 2016. The first generic entry times (December 2013, December 2012, August 2013, respectively) were regarded as the intervention time points. We estimated changes in volume and cost following the generic entry. RESULTS: We found that generic entry was associated with increases in the volume of three antineoplastic agents and decreases in their costs. In terms of volume, generic entry was associated with increases in use of capecitabine, decitabine and imatinib by 815.0 (95% CI -66.5 to 1696.5, p>0.05), 11.0 (95% CI 3.7 to 18.3, p=0.004) and 2145.5 (95% CI 1784.1 to 2506.9, p<0.001) units. The entry of generic antineoplastic drugs reduced the monthly cost trend of three agents by ¥3.1 (95% CI -¥3.6 to -¥2.6, p<0.001), ¥84.7 (95% CI -¥104.7 to -¥64.6, p<0.001) and ¥21.3 (95% CI -¥24.2 to -¥18.4, p<0.001), respectively. The entry of generic drugs attenuated the upward trend in volume of three brand-name drugs and even triggered reductions in the volume of brand-name capecitabine. The entry of generics was accompanied by significant increase of ¥2.6 in monthly brand-name decitabine cost (95% CI ¥0.2 to ¥5.1, p=0.04). CONCLUSION: Our findings suggested that entry of generic drugs impacted use and cost of antineoplastic medicines in China. Generic drugs may improve the availability and the affordability of antineoplastic agents, which would benefit more patients.

The effect of the implementation of low price medicine policy on medicine price in China: A retrospective study.

In an effort to relieve the pressure of drug shortages, the Chinese government implemented Low-price Medicines (LPM) policy to raise the price cap in July 2014. The purpose of this study is to examine the effect of the implementation of this policy on drug price in China. Price data of 491 LPM, including 218 low-price chemical medicines (LPCM) and 273 low-price traditional Chinese medicines (LPTCM), were collected from 699 hospitals. We used interrupted time series design to identify the variation of monthly Laspeyres Indexes (LI) and Paasche Indexes (PI) for LPM, LPCM, and LPTCM. The result demonstrated that although LPM expenditures increased, the proportion of LPM expenditures accounting for all medicine expenditures fell from 3.6% to 3.2%. After the implementation of LPM policy, there was a significant increasing trend in LPM-PI, LPCM-PI, and LPTCM-PI. The trend in LPM-LI and LPCM-LI was found from descending to rising. However, for LPTCM, the trend in the LI remained to decrease after the policy implementation. Despite the LPM policy had an increasing impact on the LPM drug price, the proportion of LPM expenditures accounting for all medicine expenditures did not increase. More efforts are needed in the future to promote the rational drug use in China.