Liver vessels generated from computed tomography are usually pretty small, which poses big challe... more Liver vessels generated from computed tomography are usually pretty small, which poses big challenges for satisfactory vessel segmentation, including 1) the scarcity of high-quality and large-volume vessel masks, 2) the difficulty in capturing vessel-specific features, and 3) the heavily imbalanced distribution of vessels and liver tissues. To advance, a sophisticated model and an elaborated dataset have been built. The model has a newly conceived Laplacian salience filter, highlighting vessel-like regions and suppressing other liver regions, to shape the vessel-specific feature learning and to balance vessels against others. It is further coupled with a pyramid deep learning architecture to capture various levels of features, hence the enhancement of feature formulation. Experiments show that this model markedly outperforms the state-of-the-art approaches, achieving a relative improvement of Dice score by at least 1.63% compared to the existing best model on available datasets. Mor...
Whole exome sequencing (WES) is used to identify mutations in a patient’s tumor DNA that are pred... more Whole exome sequencing (WES) is used to identify mutations in a patient’s tumor DNA that are predictive of tumor behavior, including the likelihood of response or resistance to cancer therapy. WES has a mutation limit of detection (LoD) at variant allele frequencies (VAF) of 5%. Putative mutations called at ≤ 5% VAF are frequently due to sequencing errors, therefore reporting these subclonal mutations incurs risk of significant false positives. Here we performed ~ 1000 × WES on fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissue biopsy samples from a non-small cell lung cancer patient, and identified 226 putative mutations at between 0.5 and 5% VAF. Each variant was then tested using NuProbe NGSure, to confirm the original WES calls. NGSure utilizes Blocker Displacement Amplification to first enrich the allelic fraction of the mutation and then uses Sanger sequencing to determine mutation identity. Results showed that 52% of the 226 (117) putative variants were disconfir...
Investigative Opthalmology & Visual Science, 2019
PURPOSE. To examine the role of ocular axial length as an ocular parameter for the prevalence and... more PURPOSE. To examine the role of ocular axial length as an ocular parameter for the prevalence and severity of diabetic retinopathy (DR). METHODS. The cross-sectional Kailuan Diabetic Retinopathy Study included patients with diabetes who participated in the community-based longitudinal Kailuan Study and who had undergone ocular fundus photography. The fundus photographs were graded using the Early Treatment of Diabetic Retinopathy Study criteria. RESULTS. The study included 1096 patients with diabetes (mean age: 60.8 6 9.4 years; axial length: 23.37 6 0.92 mm). In binary regression analysis, a higher DR prevalence was associated with shorter axial length (P ¼ 0.007; odds ratio [OR]: 0.81; 95% confidence interval [CI]: 0.70, 0.95) after adjusting for longer known duration of diabetes (P ¼ 0.02; OR: 1.13; 95%CI: 1.02, 1.24) and higher fasting blood glucose concentration (P < 0.001; OR: 1.38; 95%CI: 1.26, 1.52). A more severe DR stage was associated (regression coefficient r: 0.46) with shorter ocular axial length (P ¼ 0.047; standardized regression coefficient b: À0.06) after adjusting for higher fasting blood glucose (P < 0.001; b: 0.41) and longer known duration of diabetes (P ¼ 0.045; b: 0.07). Longer axial length was associated with a lower DR prevalence (P ¼ 0.003; b: À0.10) after adjusting for younger age (P < 0.001), male sex (P < 0.001), higher body mass index (P ¼ 0.016), and lower fasting blood glucose concentration (P ¼ 0.036). CONCLUSIONS. After adjusting for systemic risk factors, DR prevalence decreased by 19% (95%CI: 5, 30) for each millimeter increase in axial length. With longer axial length being a surrogate for axial myopia, the marked increase in myopia prevalence worldwide may lead to a relative decrease in the prevalence and incidence of DR in future.
The precise chronology of the fluvial terraces of the Yellow River in China is essential to under... more The precise chronology of the fluvial terraces of the Yellow River in China is essential to understand its geomorphological evolution history. More terrace ages are needed for the correlation of the terraces along the river and the construction of the longitudinal profile. In this study, seven terraces (T1–T7) in the Heiyukou area of the Jinshaan Canyon of the river were identified and were sampled for optical dating. The reliability of the ages was evaluated on the bases of bleachability, comparison of optical ages on fine and coarse grains, stratigraphic consistency of OSL ages, age distribution and geomorphological setting. The results show that the paired T2 terrace was formed at 72 ± 3 ka, and the T4, T5 strath terraces were dated to 108 ± 4 and >141 ± 4 ka, respectively. The ages for the samples from T6 and T7 were significantly underestimated, and the ‘infinitely old’ pre-Quaternary Red-Clay sample on the T7 terrace was dated to 134 ± 6 ka. The long-term river incision rat...
Cancer has been a major global health problem due to its high morbidity and mortality. While many... more Cancer has been a major global health problem due to its high morbidity and mortality. While many chemotherapy agents have been studied and applied in clinical trials or in clinic, their application is limited due to its toxic side effects and poor tolerability. Monoclonal antibodies specific to the PD-1 and PD-L1 immune checkpoints have been approved for the treatment of various tumors. However, the application of PD-1/PD-L1 inhibitors remains suboptimal and thus another strategy comes in to our sight involving the combination of checkpoint inhibitors with other agents, enhancing the therapeutic efficacy. Various novel promising approaches are now in clinical trials, just as icing on the cake. This review summarizes relevant investigations on combinatorial therapeutics based on PD-1/PD-L1 inhibition.
Background Diagnosis and follow-up of retinal diseases may be improved if the thickness of the va... more Background Diagnosis and follow-up of retinal diseases may be improved if the thickness of the various retinal layers, in addition to the total retinal thickness, is taken into account. Here we measured the thickness of the macular retinal layers in a population-based study group to assess the normative values and their associations. Methods Using spectral-domain optical coherence tomographic images, we measured the thickness of the macular retinal layers in participants of the population-based Beijing Eye Study without ocular diseases and without arterial hypertension, hyperlipidemia and diabetes mellitus. Results The study included 384 subjects (mean age:60.0±8.0 years). In multivariable analysis, the thickness of the retinal layers in the foveal region, of all retinal layers except for the outer plexiform layer in the parafoveal area, and the thickness of the ganglion cell layer, inner plexiform layer and inner and outer nuclear layer in the perifoveal area decreased with older a...
Caspofungin is an echinocandin antifungal agent licensed as a first-line therapy for invasive can... more Caspofungin is an echinocandin antifungal agent licensed as a first-line therapy for invasive candidiasis in patients with moderate to severe illness or recent exposure to azoles. In this study we developed a whole-body physiology-based pharmacokinetics (WB-PBPK) model to predict the pharmacokinetics (PK) of caspofungin, and combined with Monte Carlo simulation (MCS) to optimize clinical dosage regimens of caspofungin in different kinds of patients. A WB-PBPK model of caspofungin was built and validated with raw data from 4 previous trials of general patients, intensive care unit (ICU) patients with Child-Pugh B, ICU patients on continuous renal replacement therapy, mild and moderate hepatic insuffciency (HI) patients. MCS was used to optimize clinical dosage regimens of caspofungin in these patients. A cumulative fraction of response (CFR) value of ≥90% was considered to be the minimum for achieving optimal empirical therapy. The simulated results of the WB-PBPK model were in good ...
To assess the 10-year incidence and progression of epiretinal membranes (ERMs). The population-ba... more To assess the 10-year incidence and progression of epiretinal membranes (ERMs). The population-based longitudinal Beijing Eye Study, which included 4439 subjects (age:40+years) in 2001, was repeated in 2011 with 2695 subjects participating (66.4% of the survivors). The study participants underwent a detailed ophthalmic examination, including retinal photography. Assessing fundus photograohs, ERMs were classified as cellophane macular reflex (CMR) without retinal folds, or as preretinal macular fibrosis (PMF) without or with retinal folds. Fundus photographs were available for 2476 subjects with a mean age of 69.0±7.8 years (range:51-93 years) and mean axial length of 23.3±0.9 mm (range:19.92-26.33mm). The 10-year incidence of ERMs was 8.4% (208/2476 participants; 95% confidence interval (CI):7.4,9.5). ERMs developed bilaterally in 50 (24%) individuals and unilaterally in 158 (76%) persons. The incidence of PMFs with 2.5% (95% CI: 1.9, 3.1) was lower than the incidence of CMRs with 5...
To investigate the progression pattern of myopic maculopathy and associated factors in a populati... more To investigate the progression pattern of myopic maculopathy and associated factors in a population-based study. Population-based longitudinal study. The Beijing Eye Study including 4439 participants in 2001 was repeated in 2011, with 2695 individuals (66.4%) being re-examined in 2011. The study participants underwent detailed ophthalmic and general examinations. Using fundus photographs obtained in 2001 and 2011, we assessed the progression of myopic maculopathy in highly myopic eyes with a refractive error ≥-6 diopters in 2001. Myopic maculopathy was differentiated into tessellated fundus (category 1), diffuse chorioretinal atrophy (category 2), patchy chorioretinal atrophy (category 3), and macular atrophy (category 4), with lacquer cracks and choroidal neovascularization as additional plus signs. Progression pattern of myopic maculopathy. Of 110 highly myopic eyes (70 individuals) at baseline, 39 eyes (35.5%) showed progression observed in 15 of 79 eyes (19%) with tessellated fu...
The serum proteins creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T are classic biomar... more The serum proteins creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T are classic biomarkers of cardiac ischemic damage in clinical practice, which can sensitively detect myocardial necrosis, while other two serum proteins, ischemia-modified albumin and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have been recently identified as novel biomarkers of myocardial ischemia. In this study, the four biomarkers were detected in sera from 44 eligible patients with suspected coronary heart disease (CHD) before and after treadmill exercise test (TET), electrocardiogram (ECG) was measured during TET (TET-ECG) and invasive examination of coronary angiography (CAG), which is the 'gold standard' of CHD diagnosis, was also performed. For CAG, 25 patients were positive and 19 were negative, whereas for TET-ECG the numbers were 19 and 25, respectively. Among these four biomarkers, the NT-proBNP level in CAG positive group was much higher than those in CAG negative group both before and after TET, with statistical significance before TET (P 5 0.008). Furthermore, according to receiver operating characteristic (ROC) curve, the serum biomarker NT-proBNP showed diagnostic effect of CHD and its cutoff value was 67 pg/ml, thus 30 of the patients in this study were NT-proBNP positive and 14 were negative. And it was found that NT-proBNP obviously enhanced the sensitivity of examinations whether analyzed alone or in combination with TET-ECG. More importantly, all the patients who were negative in both NT-proBNP and TET-ECG tests turned out to be CAG negative, which means that the combination of these two non-invasive examinations might take the place of invasive examination of CAG for CHD diagnosis. Further studies with more patients are warranted to validate the findings in this paper.
The postnatal coronary vessels have been viewed as developing through expansion of vessels formed... more The postnatal coronary vessels have been viewed as developing through expansion of vessels formed during the fetal period. Using genetic lineage tracing, we found that a substantial portion of postnatal coronary vessels arise de novo in the neonatal mouse heart, rather than expanding from preexisting embryonic vasculature. Our data show that lineage conversion of neonatal endocardial cells during trabecular compaction generates a distinct compartment of the coronary circulation located within the inner half of the ventricular wall. This lineage conversion occurs within a brief period after birth and provides an efficient means of rapidly augmenting the coronary vasculature. This mechanism of postnatal coronary vascular growth provides avenues for understanding and stimulating cardiovascular regeneration following injury and disease.
Randomized start and withdrawal designs have been recently proposed to test the diseasemodifying ... more Randomized start and withdrawal designs have been recently proposed to test the diseasemodifying agents on Alzheimer's disease (AD). This article provides methods to determine the optimum parameters for these designs. A general linear mixed effects model is proposed. This model employs a piecewise linear growth pattern for those in the delayed treatment or early withdrawal arm, and incorporates a potential correlation on the rates of change on efficacy outcome before and after the treatment switch. Based on this model, we formulate the diseasemodifying hypothesis by comparing the rate of change on efficacy outcome between treatment arms with and without a treatment switch, and develop a methodology to optimally determine the sample size allocations to different treatment arms as well as the time of treatment switch for subjects whose treatment is changed. We then propose an intersection-union test (IUT) to assess the disease-modifying efficacy, and study the size and the power of the IUT. Finally, we employ two recently published symptomatic trials on AD to obtain pilot estimates to model parameters, and provide the optimum design parameters including total and individual sample size to different arms as well as the time of treatment switch for future disease-modifying trials on AD.
Science in China Series E: Technological Sciences, 2006
Based on the spatial information techniques such as RS, GIS, and GPS, the forest landscape patter... more Based on the spatial information techniques such as RS, GIS, and GPS, the forest landscape patterns in the Helan Mountain, western China, were studied. The Landsat 5 TM data were used to classify the forest landscapes through RS digital cartography, and then, the landscape characteristics and landscape pattern were analyzed quantificationally. Furthermore, through spatial data collection and spatial analysis of the main disturbances in this area, the cause of landscape formation was studied. The results showed that the total 1177 forest landscape patches could be classified into 21 landscape types, and the forest landscape in the Helan Mountain was island pattern, which was encircled by deserta as matrix. The values of landscape diversity index and landscape fragmentation index were 2.61 and 0.43, respectively. In this area, the landscape pattern was clearly formed and continuously changed in response to geological processes, climate, activities of organisms, forest fire, desertification, human activities and so on. This landscape pattern had an obviously negative effect on the stability and ecosystem services of forests. So, scientific landscape planning and protection should be adopted to improve the sustainability of forest management in this area.
The database of open-framework aluminophosphate (AlPO) syntheses has been established, which incl... more The database of open-framework aluminophosphate (AlPO) syntheses has been established, which includes about 1600 synthetic records. Data analysis has been done on the basis of the framework composition, structure dimension, pore ring, and organic template. This database will serve as useful guidance for the rational synthesis of microporous functional materials.
SUPPORTING INFORMATION Experimental Materials. 0.5, 1, 3 and 5 µm-diameter SiO 2 particles were p... more SUPPORTING INFORMATION Experimental Materials. 0.5, 1, 3 and 5 µm-diameter SiO 2 particles were purchased from MicroParticles GmbH (Germany) as a 5 wt% suspension and were used as received. Dopamine hydrochloride was purchased from Sigma-Aldrich and used as received. The solid core mesoporous shell (SC/MS) particles were prepared by the method reported by Büchel and
SARS-CoV-2 infection has become an urgent public health concern worldwide, severely affecting our... more SARS-CoV-2 infection has become an urgent public health concern worldwide, severely affecting our society and economy due to the long incubation time and high prevalence. People spare no effort on the rapid development of vaccine and treatment all over the world. Amongst the numerous ways of tackling this pandemic, some approaches using extracellular vesicles (EVs) are emerging. In this review, we summarize current prevalence and pathogenesis of COVID-19, involving the combination of SARS-CoV-2 and virus receptor ACE2, endothelial dysfunction and micro thrombosis, together with cytokine storm. We also discuss the ongoing EVs-based strategies for the treatment of COVID-19, including mesenchymal stem cell (MSC)-EVs, drug-EVs, vaccine-EVs, platelet-EVs, and others. This manuscript provides the foundation for the development of targeted drugs and vaccines for SARS-CoV-2 infections.
Evidence-based complementary and alternative medicine : eCAM, 2018
BuqiHuoxueTongluo Formula (BHTF) is an effective herbal prescription based on traditional Chinese... more BuqiHuoxueTongluo Formula (BHTF) is an effective herbal prescription based on traditional Chinese medicine for idiopathic pulmonary fibrosis (IPF). The aim of this study was to elucidate the influence of BHTF on induced IPF model through the aspect of histopathology and pulmonary function test. Wistar rats with bleomycin-induced IPF were given BHTF via intragastric gavage. After 14 days and 28 days of treatment, respectively, on these two time points, we first performed pulmonary function test, performed ventilation measure, and traced the Pressure-Volume Loop under anesthesia. Then, rats were sacrificed for hematoxylin-eosin and Masson's trichrome staining, immunohistochemistry staining of TGF- and -SMA, and observation through transmission electron microscope. BHTF reduced infiltration of inflammation cells, collagen deposition, and fibrosis proliferation in pulmonary mesenchyme, inhibited the expression of TGF- and -SMA, and avoided the abnormality of ultrastructure and quant...
Normal epithelial tissue exerts an intrinsic tumor-suppressive effect against oncogenically trans... more Normal epithelial tissue exerts an intrinsic tumor-suppressive effect against oncogenically transformed cells. In Drosophila imaginal epithelium, clones of oncogenic polarity-deficient cells mutant for scribble (scrib) or discs large (dlg) are eliminated by cell competition when surrounded by wild-type cells. Here, through a genetic screen in Drosophila, we identify Serpin5 (Spn5), a secreted negative regulator of Toll signaling, as a crucial factor for epithelial cells to eliminate scrib mutant clones from epithelium. Downregulation of Spn5 in wild-type cells leads to elevation of Toll signaling in neighboring scrib cells. Strikingly, forced activation of Toll signaling or Toll-related receptor (TRR) signaling in scrib clones transforms scrib cells from losers to supercompetitors, resulting in tumorous overgrowth of mutant clones. Mechanistically, Toll activation in scrib clones leads to c-Jun N-terminal kinase (JNK) activation and F-actin accumulation, which cause strong activatio...
Choroidal neovascularization (CNV) is a severe eye disease that leads to blindness, especially in... more Choroidal neovascularization (CNV) is a severe eye disease that leads to blindness, especially in the elderly population. Various endogenous and exogenous regulatory factors promote its pathogenesis. However, the detailed molecular biological mechanisms of CNV have not been fully revealed. In this study, by using advanced computational tools, a number of key gene ontology (GO) terms and KEGG pathways were selected for CNV. A total of 29 validated genes associated with CNV and 17,639 nonvalidated genes were encoded based on the features derived from the GO terms and KEGG pathways by using the enrichment theory. The widely accepted feature selection method-maximum relevance and minimum redundancy (mRMR)-was applied to analyze and rank the features. An extensive literature review for the top 45 ranking features was conducted to confirm their close associations with CNV. Identifying the molecular biological mechanisms of CNV as described by the GO terms and KEGG pathways may contribute ...
Uploads
Papers by Yan Yan