Nanjing Children's Hospital

Mitochondrial dysfunction has gained recognition as a contributing factor in many diseases. The kidney is a kind of organ with high energy demand, rich in mitochondria. As such, mitochondrial dysfunction in the kidney plays a critical role in the pathogenesis of kidney diseases. Despite the recognized importance mitochondria play in the pathogenesis of the diseases, there is limited understanding of various aspects of mitochondrial biology. This review examines the physiology and pathophysiology of mitochondria. It begins by discussing mitochondrial structure, mitochondrial DNA, mitochondrial reactive oxygen species production, mitochondrial dynamics, and mitophagy, before turning to inherited mitochondrial cytopathies in kidneys (inherited or sporadic mitochondrial DNA or nuclear DNA mutations in genes that affect mitochondrial function). Glomerular diseases, tubular defects, and other renal diseases are then discussed. Next, acquired mitochondrial dysfunction in kidney diseases is discussed, emphasizing the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease and acute kidney injury, as their prevalence is increasing. Finally, it summarizes the possible beneficial effects of mitochondrial-targeted therapeutic agents for treatment of mitochondrial dysfunction-mediated kidney injury-genetic therapies, antioxidants, thiazolidinediones, sirtuins, and resveratrol-as mitochondrial-based drugs may offer potential treatments for renal diseases.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

BACKGROUND: The prevalence of sensitization in patients with asthma and rhinitis in mainland China remains unclear. OBJECTIVE: Our aim was to estimate the prevalence of allergy in patients with respiratory allergic diseases such as asthma and/or rhinitis attending respiratory clinics within mainland China. The study also investigated regional and annual differences in the prevalence and pattern of sensitization among the patients in China. METHOD: A cross-sectional survey was performed in 6304 patients suffering from asthma and/or rhinitis in 17 cities from 4 regions of China. Patients completed a standardized questionnaire asking for the presence of respiratory and allergic symptoms. They also underwent skin prick tests with 13 common aeroallergens. RESULTS: Among the 6304 patients, 4545 (72.1%) had at least one positive skin prick reaction. The overall prevalence of positive skin prick responses was 59.0% for Dermatophagoides farinae, 57.6% for Dermatophagoides pteronyssinus, 40.7% for Blomia tropicalis, 16.1% for American cockroach, 14.0% for dog, 11.5% for Blatella germanica, 11.3% for Artemisia vulgaris, 10.3% for cat, 6.5% for Ambrosia artemisifolia, 6.3% for mixed mould I, 4.4% for mixed mould IV, 3.5% for mixed grass pollen and 2.2% for mixed tree pollen. Sensitizations to common allergens varied widely between geographical areas and demonstrated unique pattern in patients by stratification with age groups, with asthma and/or rhinitis. Severity of rhinitis and asthma was significantly correlated with skin index of reactivity to Artemisia vulgaris, Ambrosia artemisifolia and to D. pteronyssinus, D. farinae and Blomia tropicalis respectively (P < 0.001). Positive reactivity to the tested allergens and concomitant reactivity to multiple allergens including to house dust mites and Blomia tropicalis was markedly increased in patients with both asthma and rhinitis. CONCLUSION: House dust mites were the most prevalent allergens in patients with asthma and/or rhinitis in China. There were significant differences in patterns of sensitizations in patients from different geographical areas, age groups as well as asthma and/or rhinitis.

Background: Congenital birth defects (CBDs) present enormous challenges to global healthcare systems. These conditions severely impact patients' health and underscore issues related to socioeconomic development and healthcare accessibility and efficiency. Previous studies have been geographically limited and lacked comprehensive global analysis. This study provides global, regional, and national disability-adjusted life years (DALYs) data for four major congenital birth defects-congenital heart defects (CHD), neural tube defects (NTDs), digestive congenital anomalies (DCAs), and Down syndrome (DS) from 1990 to 2021, emphasizing health inequalities. The goal is to offer scientific evidence for optimizing resource allocation, focusing on high-burden populations, and reducing disease burden. Methods: This study systematically evaluated the global, regional, and national burden of CBDs and their changes from 1990 to 2021 using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. To conduct a more focused analysis, four specific CBDs were selected: CHD, NTDs, DCAs, and DS. DALYs were used as the metric, combined with the sociodemographic index (SDI). Analyses included the slope index of inequality and concentration index to measure health inequalities, frontier analysis to estimate achievable outcomes based on development levels, decomposition analysis to identify drivers of disease burden changes, Joinpoint regression analysis to assess temporal trends, and the Bayesian age-period-cohort (BAPC) model to predict future disease burden trends. Findings: Compared to 1990, the global burden of the CBDs in 2021 showed a downward trend. Males had a higher burden than females, with the highest burden observed in low-SDI regions. When examining CHD, NTDs, DCAs, and DS specifically, trends in burden changes varied across different CBDs at the global, regional, and national levels. Frontier analysis revealed potential for burden improvement in various countries and territories. Decomposition analysis highlighted differences in disease burden drivers across SDI regions, showing the greatest improvement observed in low-SDI regions. Joinpoint regression analysis indicated a downward trend in DALYs burden across SDI regions, and BAPC model predictions suggested that the burden of CBDs will continue to decline in the future. Interpretation: CBDs pose a major challenge to global public health. Despite an overall decline in disease burden, health inequalities remain prominent, particularly in countries and territories with lower levels of development. Future public health interventions should focus on countries and territories with low levels of development by optimizing healthcare resource allocation, improving basic health infrastructure, enhancing health education, and reducing disease burden inequalities. Global collaboration and data sharing are essential to promote a lifecycle management model for CBDs research and treatment, advancing global health development. Funding: This study was supported by the National Natural Science Foundation of China (No. 82270310) and the Jiangsu Provincial Key Research and Development Program (No. BE2023662).

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING: Gates Foundation.

Respiratory syncytial virus is a leading cause of lower respiratory tract illness among infants, the elderly and immunocompromised individuals. Currently, there is no effective vaccine or disease modifying treatment available and novel interventions are urgently required. Cathelicidins are cationic host defence peptides expressed in the inflamed lung, with key roles in innate host defence against infection. We demonstrate that the human cathelicidin LL-37 has effective antiviral activity against RSV in vitro, retained by a truncated central peptide fragment. LL-37 prevented virus-induced cell death in epithelial cultures, significantly inhibited the production of new infectious particles and diminished the spread of infection, with antiviral effects directed both against the viral particles and the epithelial cells. LL-37 may represent an important targetable component of innate host defence against RSV infection. Prophylactic modulation of LL-37 expression and/or use of synthetic analogues post-infection may represent future novel strategies against RSV infection.

In order to detect multiple sclerosis (MS) subjects from healthy controls (HCs) in magnetic resonance imaging, we developed a new system based on machine learning. The MS imaging data was downloaded from the eHealth laboratory at the University of Cyprus, and the HC imaging data was scanned in our local hospital with volunteers enrolled from community advertisement. Inter-scan normalization was employed to remove the gray-level difference. We adjust the misclassification costs to alleviate the effect of unbalanced class distribution to the classification performance. We utilized two-level stationary wavelet entropy (SWE) to extract features from brain images. Then, we compared three machine learning based classifiers: the decision tree, k-nearest neighbors (kNN), and support vector machine. The experimental results showed the kNN performed the best among all three classifiers. In addition, the proposed SWE+kNN approach is superior to four state-of-the-art approaches. Our proposed MS detection approach is effective.

Pyroptosis, one kind of inflammatory regulated cell death, is involved in various inflammatory diseases, including acute kidney injury (AKI). Besides Gasdermin D (GSDMD), GSDME is a newly identified mediator of pyroptosis via the cleavage of caspase-3 generating pyroptotic GSDME-N. Here, we investigated the role of GSDME in renal cellular pyroptosis and AKI pathogenesis employing GSDME-deficient mice and human tubular epithelial cells (TECs) with the interventions of pharmacological and genetic approaches. After cisplatin treatment, GSDME-mediated pyroptosis was induced as shown by the characteristic pyroptotic morphology in TECs, upregulated GSDME-N expression and enhanced release of IL-1β and LDH, and decreased cell viability. Strikingly, silencing GSDME in mice attenuated acute kidney injury and inflammation. The pyroptotic role of GSDME was also verified in human TECs in vitro. Further investigation showed that inhibition of caspase-3 blocked GSDME-N cleavage and attenuated cisplatin-induced pyroptosis and kidney dysfunction. Moreover, deletion of GSDME also protected against kidney injury induced by ischemia-reperfusion. Taken together, the findings from current study demonstrated that caspase-3/GSDME-triggered pyroptosis and inflammation contributes to AKI, providing new insights into the understanding and treatment of this disease.

AIM: To investigate the effect of a new infant formula supplemented with a low level (0.24 g/100 mL) of galacto-oligosaccharide (GOS) on intestinal micro-flora (Bifidobacteria, Lactobacilli and E. coli) and fermentation characteristics in term infants, compared with human milk and a standard infant formula without GOS. METHODS: Term infants (n = 371) were approached in this study in three hospitals of China. All infants started breast-feeding. Those who changed to formula-feeding within 4 wk after birth were randomly assigned to one of the two formula groups. Growth and stool characteristics, and side effects that occurred in recruited infants were recorded in a 3-mo follow-up period. Fecal samples were collected from a subpopulation of recruited infants for analysis of intestinal bacteria (culture technique), acetic acid (gas chromatography) and pH (indicator strip). RESULTS: After 3 mo, the intestinal Bifidobacteria, Lactobacilli, acetic acid and stool frequency were significantly increased, and fecal pH was decreased in infants fed with the GOS-formula or human milk, compared with those fed with the formula without GOS. No significant differences were observed between the GOS formula and human milk groups. Supplementation with GOS did not influence the incidence of crying, regurgitation and vomiting. CONCLUSION: A low level of GOS (0.24 g/100 mL) in infant formula can improve stool frequency, decrease fecal pH, and stimulate intestinal Bifidobacteria and Lactobacilli as in those fed with human milk.

The increasing amount of particulate matter (PM) in the ambient air is a pressing public health issue globally. Epidemiological studies involving data from millions of patients or volunteers have associated PM with increased risk of dementia and Alzheimer's disease in the elderly and cognitive dysfunction and neurodegenerative pathology across all age groups, suggesting that PM may be a risk factor for neurodegenerative diseases. Neurodegenerative diseases affect an increasing population in this aging society, putting a heavy burden on economics and family. Therefore, understanding the mechanism by which PM contributes to neurodegeneration is essential to develop effective interventions. Evidence in human and animal studies suggested that PM induced neurodenegerative-like pathology including neurotoxicity, neuroinflammation, oxidative stress, and damage in blood-brain barrier and neurovascular units, which may contribute to the increased risk of neurodegeneration. Interestingly, antagonizing oxidative stress alleviated the neurotoxicity of PM, which may underlie the essential role of oxidative stress in PM's potential effect in neurodegeneration. This review summarized up-to-date epidemiological and experimental studies on the pathogenic role of PM in neurodegenerative diseases and discussed the possible underlying mechanisms.

BACKGROUND: Over the last few decades, there has been a worldwide epidemic of childhood obesity. An important step in successful prevention in paediatrics is the identification of modifiable risk factors of childhood obesity. Many studies have evaluated the associations between television (TV) watching and childhood obesity but yielded inconsistent results. METHODS: To help elucidate the role of TV watching, PubMed and Embase databases were searched for published studies on associations between TV watching and childhood obesity. Random-effects models and dose-response meta-analyses were used to pool study results. RESULTS: Fourteen cross-sectional studies with 24 reports containing 106 169 subjects were included in the meta-analysis. Subgroup analyses were conducted by the available characteristics of studies and participants. The multivariable-adjusted overall OR of the childhood obesity for the highest vs. the lowest time of TV watching was 1.47 [95% confidence interval (95% CI): 1.33-1.62]. A linear dose-response relationship was also found for TV watching and childhood obesity (P < 0.001), and the risk increased by 13% for each 1 h/day increment in TV watching. Subgroup analysis showed a basically consistent result with the overall analysis. The association is observed in both boys and girls (for boys, OR 1.30, 95% CI 1.16-1.45; for girls, OR 1.26, 95% CI 1.11-1.41). CONCLUSIONS: our meta-analysis suggested that increased TV watching is associated with increased risk of childhood obesity. And restricting TV time and other sedentary behaviour of children may be an important public health strategy to prevent childhood obesity.

(Aim) Classification of brain images as pathological or healthy case is a key pre-clinical step for potential patients. Manual classification is irreproducible and unreliable. In this study, we aim to develop an automatic classification system of brain images in magnetic resonance imaging (MRI). (Method) Three datasets were downloaded from the Internet. Those images are of T2-weighted along axial plane with size of 256 × 256. We utilized an s-level decomposition on the basis of dual-tree complex wavelet transform (DTCWT), in order to obtain 12s “variance and entropy (VE)” features from each subband. Afterwards, we used support vector machine (SVM) and its two variants: the generalized eigenvalue proximal SVM (GEPSVM) and the twin SVM (TSVM), as the classifiers. In all, we proposed three novel approaches: DTCWT + VE + SVM, DTCWT + VE + GEPSVM, and DTCWT + VE + TSVM. (Results) The results showed that our “DTCWT + VE + TSVM” obtained an average accuracy of 99.57%, which was not only better than the two other proposed methods, but also superior to 12 state-of-the-art approaches. In addition, parameter estimation showed the classification accuracy achieved the largest when the decomposition level s was assigned with a value of 1. Further, we used 100 slices from real subjects, and we found our proposed method was superior to human reports from neuroradiologists. (Conclusions) This proposed system is effective and feasible.

Exosomes can transfer genetic materials between cells. Their roles in viral infections are beginning to be appreciated. Researches have shown that exosomes released from virus-infected cells contain a variety of viral and host cellular factors that are able to modulate recipient's cellular response and result in productive infection of the recipient host. Here, we showed that EV71 infection resulted in upregulated exosome secretion and differential packaging of the viral genomic RNA and miR-146a into exosomes. We provided evidence showing that miR-146a was preferentially enriched in exosomes while the viral RNA was not in infected cells. Moreover, the exosomes contained replication-competent EV71 RNA in complex with miR-146a, Ago2, and GW182 and could mediate EV71 transmission independent of virus-specific receptor. The exosomal viral RNA could be transferred to and replicate in a new target cell while the exosomal miR-146a suppressed type I interferon response in the target cell, thus facilitating the viral replication. Additionally, we found that the IFN-stimulated gene factors (ISGs), BST-2/tetherin, were involved in regulating EV71-induced upregulation of exosome secretion. Importantly, in vivo study showed that exosomal viral RNA exhibited differential tissue accumulation as compared to the free virus particles. Together, our findings provide evidence that exosomes secreted by EV71-infected cells selectively packaged high level miR-146a that can be functionally transferred to and facilitate exosomal EV71 RNA to replicate in the recipient cells by suppressing type I interferon response.

Myocardial infarction (MI) is one of the leading causes of morbidity and mortality world-wide. Whether endogenous repair and regenerative ability could be augmented by drug administration is an important issue for generation of novel therapeutic approach. Recently it was reported that in mice pretreated with thymosin beta 4 (TB4) and subsequently subjected to experimental MI, a subset of epicardial cells differentiated into cardiomyocytes. In clinical settings, epicardial priming with TB4 prior to MI is impractical. Here we tested if TB4 treatment after MI could reprogram epicardium into cardiomyocytes and augment the epicardium's injury response. Using epicardium genetic lineage trace line Wt1(CreERT2/+) and double reporter line Rosa26(mTmG/+), we found post-MI TB4 treatment significantly increased the thickness of epicardium and coronary capillary density. However, epicardium-derived cells did not adopt cardiomyocyte fate, nor did they migrate into myocardium to become coronary endothelial cells. Our result thus indicates that TB4 treatment after MI does not alter epicardial cell fate to include the cardiomyocyte lineage, providing both cautions and insights for the full exploration of the potential benefits of TB4 in the clinical settings. This article is part of a Special Issue entitled 'Possible Editorial'.

The International Agency for Research on Cancer and the World Health Organization have designated airborne particulates, including particulates of median aerodynamic diameter ≤ 2.5 μm (PM2.5), as Group 1 carcinogens. It has not been determined, however, whether exposure to ambient PM2.5 is associated with an increase in respiratory related diseases. This meta-analysis assessed the association between exposure to ambient fine particulate matter (PM2.5) and the risk of respiratory tract diseases, using relevant articles extracted from PubMed, Web of Science, and Embase. In results, of the 1,126 articles originally identified, 35 (3.1%) were included in this meta analysis. PM2.5 was found to be associated with respiratory tract diseases. After subdivision by age group, respiratory tract disease, and continent, PM2.5 was strongly associated with respiratory tract diseases in children, in persons with cough, lower respiratory illness, and wheezing, and in individuals from North America, Europe, and Asia. The risk of respiratory tract diseases was greater for exposure to traffic related than non-traffic-related air pollution. In children, the pooled relative risk (RR) represented significant increases in wheezing (8.2%), cough (7.5%), and lower respiratory illness (15.3%). The pooled RRs in children were 1.091 (95%CI: 1.049, 1.135) for exposure to < 25 μg/m3 PM2.5, and 1.126 (95%CI: 1.067, 1.190) for exposure to ≥ 25 μg/m3 PM2.5. In conclusion, exposure to ambient PM2.5 was significantly associated with the development of respiratory tract diseases, especially in children exposed to high concentrations of PM2.5.

BACKGROUND: Oligosaccharides in human milk may protect infants by improving the intestinal micro-flora and fermentation. This study was to investigate effects of infant formula milk consisting of galacto-oligosaccharide (GOS) on intestinal microbial populations and the fermentation characteristics in term infants in comparison with that of human milk. METHODS: The test formula (Frisolac H, Friesland, Netherland) was supplemented with GOS at a concentration of 0.24 g/dl. Human milk and another formula without oligosaccharides (Frisolac H, Friesland, Netherland) were used as positive and negative control respectively. Growth, stool characteristics, and side effects of the recruited infants were recorded after 3 and 6 months' follow-up, and the fecal species were collected for the analysis of intestinal micro-flora, short chain fatty acid (SCFA) and pH. RESULTS: At the end of 3- and 6-month feeding period, intestinal Bifidobacteria and Lactobacilli were significantly increased in infants fed with GOS supplemented formula and human milk when compared with infants fed with negative control formula; however, there was no statistically significant difference between GOS supplemented formula and human milk groups. Stool characteristics were influenced by the supplement and main fecal SCFA (acetic), and stool frequency were significantly increased in infants fed with GOS supplemented formula and human milk, while the fecal pH was significantly decreased as compared with that of negative control (P < 0.05). Supplementation had no influence on incidence of side effects (including crying, regurgitation and vomiting). CONCLUSIONS: Supplementing infant formula with GOS at a concentration of 0.24 g/dl stimulates the growth of Bifidobacteria and Lactobacilli in the intestine and stool characteristics are similar to in term infants fed with human milk.

BACKGROUND: In China, there were few studies about the pathogens of acute viral encephalitis and meningitis in children in recent years. The aims of this study were to characterize the etiology and prognosis of acute viral encephalitis and meningitis in Chinese children. METHODS: This was a multicentre prospective study. Two hundred and sixty one viral encephalitis patients and 285 viral meningitis patients were enrolled. The mean age of viral encephalitis and meningitis were 5.88 ± 3.60 years and 6.39 ± 3.57 years, respectively. Real-time reverse transcription PCR and multiplex PCR were used to detect human enteroviruses and herpes viruses in cerebrospinal fluid (CSF) of patients with encephalitis or meningitis. The enzyme-linked immune absorbent assay (ELISA) was used for detecting IgM antibody against Japanese encephalitis virus (JEV) in CSF and against mumps virus, tick-borne encephalitis virus (TBEV), dengue virus and rubella virus in acute serum. The clinical and outcome data were collected during patients' hospitalization. RESULTS: The etiology of viral encephalitis was confirmed in 52.5% patients. The primary pathogen was human enteroviruses (27.7%) in viral encephalitis. The incidence of sequelae and the fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The etiology of viral meningitis was identified in 42.8% cases. The leading pathogen was also human enteroviruses (37.7%) in viral meningitis. The prognosis of viral meningitis was favorable with only 0.7% patients had neurological sequelae. CONCLUSIONS: Human enteroviruses were the leading cause both in acute viral encephalitis and viral meningitis in children. The incidence of sequelae and fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The prognosis of viral meningitis was favorable compared to viral encephalitis.

BACKGROUND: -NPs-exposure on behavior, neuropathology, and synapse in young adult mice and primary cortical neuron cultures. RESULTS: -NPs (NP) using intranasal instillation. Behavioral tests were performed after 1 and 2 months of exposure. We observed decreased social activity at both time points as well as anxiety and cognitive impairment after 2 months in the NP-exposed mice. NP deposition was primarily detected in the medial prefrontal cortex and the hippocampus. Neurodegeneration-like pathological changes, including reduced Nissl staining, increased tau phosphorylation, and neuroinflammation, were also present in the brains of NP-exposed mice. Furthermore, we observed NP-induced impairment in exocytosis along with decreased synapsin I and increased synaptophysin expression in the synaptosome fractions isolated from the frontal cortex as well as primary neuronal cultures. Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were also activated in the frontal cortex of NP-exposed mice. Moreover, inhibition of ERK activation prevented NP-mediated changes in exocytosis in cultured neurons, highlighting a key role in the changes induced by NP exposure. CONCLUSIONS: -NPs results in mood dysfunction and cognitive impairment in young adult mice and causes neurodegeneration-like pathology and synaptic changes via ERK activation.

Long non-coding RNA (lncRNA) was referred to be participating in various malignant tumors. Location based analysis of the mechanism in lncRNA and genes have been highly focused. In this study, we reported that lncRNA named NALT which was located near NOTCH1 within 100 bp away. We confirmed that up-regulation of NALT associating with NOTCH1 in human samples. Increased expression of NALT dramatically promoted cell proliferation in cell lines via CCK8 assay and EDU stain. Further xenograft tumor also indicated the growth inducing affection of NALT while could be partial reversed by GSI. Besides, through sorting the side-population cells in T ALL cells treated with NALT shRNA could decrease percentage of SP cell which companied by the down-regulation of NOTCH1. Gal4-λN/BoxB reporter system revealed that the nuclear located NALT could function as a transcription activator which caused an activation of NOTCH signal pathway as confirmed by western blot. Taken together, we found a neighbor of NOTCH1, Lnc-RP11-611D20.2 (named NALT) which could regulate the NOTCH1 signal pathway through cis-regulation. This founding may trigger a comparable development of diagnosis or novel molecularly-directed therapies.

BACKGROUND: MicroRNAs (miRNAs) are present in body fluids and may have the potential to serve as disease biomarkers. This study explored the clinical value of miRNAs in serum and urine as biomarkers for idiopathic childhood nephrotic syndrome (NS). METHODS: We obtained serum samples from 159 NS children (24 steroid resistant and 135 steroid sensitive), 109 age/sex-matched healthy controls and 44 children with other kidney diseases. Serum miRNAs were analyzed with the TaqMan Low Density Array and then validated with a quantitative reverse-transcription PCR assay with 126 individual samples. Moreover, we collected paired serum samples from 50 patients before and after treatment to determine the value of these miRNAs for condition assessment. In addition, urine samples from these patients were examined for candidate miRNAs. RESULTS: The concentrations of serum miR-30a-5p, miR-151-3p, miR-150, miR-191, and miR-19b were highly increased in NS children compared with controls (P < 0.0001). The urinary miR-30a-5p concentration was also increased in NS (P = 0.001). The area under the ROC curve and the odds ratio for the combined 5 serum miRNAs were 0.90 (95% CI, 0.86-0.94; P < 0.0001) and 40.7 (95% CI, 6.06-103; P < 0.0001), respectively. Moreover, the concentrations of the 5 serum miRNAs and urinary miR-30a-5p markedly declined with the clinical improvement of the patients. CONCLUSIONS: We determined that 5 distinct serum miRNAs and urinary miR-30a-5p were increased in NS children. These circulating or urinary miRNAs may represent potential diagnostic and prognostic biomarkers for idiopathic pediatric NS.