This study tested whether the soluble (s)ST2 is a superb biomarker predictive of moderate to severe cerebral-cardiac syndrome (CCS) (defined as coexisting National Institute of Health Stroke Scale ...(NIHSS) >8 and left-ventricular ejection fraction (LVEF) <60%) in patients after acute ischemic stroke (IS). Between November 2015 and October 2017, a total of 99 IS patients were prospectively enrolled and categorized into three groups based on NIHSS, i.e., group 1 (NIHSS ≤ 8,
= 66), group 2 (NIHSS = 9-15,
= 14) and group 3 (NIHSS ≥ 16,
= 19), respectively. Blood samples were collected immediately after hospitalization, followed by transthoracic echocardiographic examination. The results showed that the flow cytometric analysis for assessment of inflammatory biomarkers of TLR2+/CD14+cells, TLR4+/CD14+cells, Ly6g+/CD14+cells, and MPO+/CD14+cells, and ELISA assessment for circulatory level of sST2 were significantly higher in groups 2/3 than in group 1 (all
< 0.01). However, these parameters did not show significant differences between groups 2 and 3 (all
> 0.05). The LVEF was significantly lower in group 3 than in group 1 (
< 0.001), but it displayed no difference between groups 1/2 or between groups 2/3. These inflammatory biomarkers ((TLR2+/CD14+cells// TLR4+/CD14+cells// MPO+/CD14+cells) and sST2)) were significantly positively correlated to NIHSS and strongly negatively correlated to LVEF (all
< 0.05). Multivariate analysis demonstrated that both MPO/CD14+cells >20% (
= 0.027) and sST2 ≥ 17,600 (
= 0.004) were significantly and independently predictive of moderate-severe CCS after acute IS. Receiver operating characteristic curve analysis demonstrated that sST2 was the most powerful predictor of CCS with a sensitivity of 0.929 and a specificity of 0.731 (
< 0.001). In conclusion, sST2 is a useful biomarker for prediction of CCS severity in patients after acute IS.
Highlights • 95 Raman spectra of uranium ore concentrates were analyzed by PCA, PLS-DA and FDA. • PCA, PLS-DA and FDA showed consistent and corroborating results. • Some samples of ADU and UH could ...not be distinguished from each other. • Other classes of compounds were generally well separated.
Platelet-derived growth factor is one of the major growth factors found in human and mammalian serum and tissues. Abnormal activation of platelet-derived growth factor signaling pathway through ...platelet-derived growth factor receptors may contribute to the development and progression of pulmonary vascular remodeling and obliterative vascular lesions in patients with pulmonary arterial hypertension. In this study, we examined the expression of platelet-derived growth factor receptor isoforms in pulmonary arterial smooth muscle and pulmonary arterial endothelial cells and investigated whether platelet-derived growth factor secreted from pulmonary arterial smooth muscle cell or pulmonary arterial endothelial cell promotes pulmonary arterial smooth muscle cell proliferation. Our results showed that the protein expression of platelet-derived growth factor receptor α and platelet-derived growth factor receptor β in pulmonary arterial smooth muscle cell was upregulated in patients with idiopathic pulmonary arterial hypertension compared to normal subjects. Platelet-derived growth factor activated platelet-derived growth factor receptor α and platelet-derived growth factor receptor β in pulmonary arterial smooth muscle cell, as determined by phosphorylation of platelet-derived growth factor receptor α and platelet-derived growth factor receptor β. The platelet-derived growth factor-mediated activation of platelet-derived growth factor receptor α/platelet-derived growth factor receptor β was enhanced in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell compared to normal cells. Expression level of platelet-derived growth factor-AA and platelet-derived growth factor-BB was greater in the conditioned media collected from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell than from normal pulmonary arterial endothelial cell. Furthermore, incubation of idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell with conditioned culture media from normal pulmonary arterial endothelial cell induced more platelet-derived growth factor receptor α activation than in normal pulmonary arterial smooth muscle cell. Accordingly, the conditioned media from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell resulted in more pulmonary arterial smooth muscle cell proliferation than the media from normal pulmonary arterial endothelial cell. These data indicate that (a) the expression and activity of platelet-derived growth factor receptor are increased in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell compared to normal pulmonary arterial smooth muscle cell, and (b) pulmonary arterial endothelial cell from idiopathic pulmonary arterial hypertension patients secretes higher level of platelet-derived growth factor than pulmonary arterial endothelial cell from normal subjects. The enhanced secretion (and production) of platelet-derived growth factor from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell and upregulated platelet-derived growth factor receptor expression (and function) in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell may contribute to enhancing platelet-derived growth factor/platelet-derived growth factor receptor-associated pulmonary vascular remodeling in pulmonary arterial hypertension.
Objective We aimed to examine the current developments and challenges confronted by old age security in rural China. Data sources This study is based on the data from PubMed, Elsevier, Wiley, EBSCO, ...EMBASE, SCI Expanded, ProQuest, Google, and CNKI which is the most informative database in Chinese. Study selection Articles were selected with the search terms ＂rural＂, ＂China＂, ＂old＂, ＂older＂, or ＂elder＂, ＂elderly＂, or ＂aged＂, ＂aging＂, ＂security＂, ＂culture＂, ＂value＂, ＂medical insurance＂ or ＂community based medical insurance＂ or ＂cooperative medical scheme＂. Related websites and yearbooks were searched as well. Results The socio-economic development has made the burden of traditional care for the rural elderly heavier than ever, and new challenges are emerging in rural communities, such as poor economic, deteriorating natural environment and health crisis. Conclusions The governments should improve the scale and caliber of rural old age security and strengthen regulations with areat efforts in develoDina the rural economv and Drotectina the natural environment of rural communities.
Abstract Objectives This paper investigates discriminating tongue features to distinguish between early stage breast cancer (BC) patients and non-breast cancer individuals through non-invasive ...traditional Chinese medicine (TCM) tongue diagnosis. Design The tongue features for 67 patients with 0 and 1 stages of BC, and 70 non-breast cancer individuals are extracted by the automatic tongue diagnosis system (ATDS). A total of nine tongue features, namely, tongue color, tongue quality, tongue fissure, tongue fur, red dot, ecchymosis, tooth mark, saliva, and tongue shape are identified for each tongue. Features extracted are further sub-divided according to the areas located, i.e., spleen–stomach, liver–gall-left, liver–gall-right, kidney, and heart–lung areas. This study focuses on deriving significant tongue features ( p < 0.05) to discriminate early-stage BC patients from non-breast cancer individuals. Results The Mann–Whitney test shows that the amount of tongue fur ( p = 0.024), maximum covering area of tongue fur ( p = 0.009), thin tongue fur ( p = 0.009), the average area of red dot ( p = 0.049), the maximum area of red dot ( p = 0.009), red dot in the spleen–stomach area ( p = 0.000), and red dot in the heart–lung area ( p = 0.000) demonstrate significant differences. The data collected are further classified into two groups. The training group consists of 57 early-stage BC patients and 60 non-breast cancer individuals, while the testing group is composed of 10 early-stage BC patients and 10 non-breast cancer individuals. The logistic regression by utilizing these 7 tongue features with significant differences in Mann–Whitney test as factors is performed. In order to reduce the number of tongue features employed in prediction, tongue features with the least amount of significant difference, namely, maximum area of red dot and average area of red dot, are removed progressively. The tongue features of the testing group are employed in the aforementioned three models to test the power of significant tongue features identified in predicting early-stage BC. An accuracy of 80%, 80% and 90% is reached on non-breast cancer individuals by applying the 7, 6 and 5 significant tongue features obtained through Mann–Whitney test, respectively, while 60%, 60% and 50% is reached on the corresponding early-stage BC patients. Conclusion The TCM tongue diagnosis can serve as a preliminary screening procedure in the early detection of BC in light of its simple and non-invasive nature, followed by other more accurate testing process. To the best of our knowledge, this is the first attempt in applying non-invasive TCM tongue diagnosis to the discrimination of early-stage BC patients and non-breast cancer individuals.
Self-labeling proteins have revolutionized super-resolution and sensor imaging. Tags recognize a bioorthogonal substrate for covalent attachment. We show the small Ultra-Red Fluorescent Protein ...(smURFP) is a self-labeling protein. The substrate is fluorogenic, fluoresces when attached, and quenches fluorescent cargo. The smURFP-tag has novel properties for tool development.
We developed a unique self-labeling protein based on the small Ultra-Red Fluorescent Protein and named the smURFP-tag. Biliverdin is fluorogenic, fluoresces when covalently attached, and quenches fluorescent cargo.
BACKGROUND The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging. AIM To investigate whether combined adipose-derived ...mesenchymal-stem-cells (ADMSCs)-derived exosome (EXAD) and exogenous mitochondria (mitoEx) protect the lung from ARDS complicated by SS. METHODS In vitro study, including L2 cells treated with lipopolysaccharide (LPS) and in vivo study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EXAD), 4 (ARDS-SS + mitoEx), and 5 (ARDS-SS + EXAD + mitoEx), were included in the present study. RESULTS In vitro study showed an abundance of mitoEx found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels (P < 0.001). The protein levels of inflammation interleukin (IL)-1β/tumor necrosis factor (TNF)-α/nuclear factor-κB/toll-like receptor (TLR)-4/matrix-metalloproteinase (MMP)-9/oxidative-stress (NOX-1/NOX-2)/apoptosis (cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase) were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EXAD treatment than without EXAD treatment, whereas the protein expressions of cellular junctions occluding/β-catenin/zonula occludens (ZO)-1/E-cadherin exhibited an opposite pattern of inflammation (all P < 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+/CD14+/CD68+/CD11b/c+/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all P < 0.0001), whereas arterial oxygen-saturation (SaO2%) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers (CD68+/γ-H2AX) displayed an identical pattern of SaO2% among the groups (all P < 0.0001). The protein expressions of inflammatory (TLR-4/MMP-9/IL-1β/TNF-α)/oxidative stress (NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged (cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic (beclin-1/Atg-5/ratio of LC3B-II/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants nuclear respiratory factor (Nrf)-1/Nrf-2/cellular junctions (ZO-1/E-cadherin)/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all P < 0.0001). CONCLUSION Combined EXAD-mitoEx therapy was better than merely one for protecting the lung against ARDS-SS induced injury.
Tongue diagnosis is an important practice in traditional Chinese medicine (TCM) for diagnosing diseases before determining proper means of treatments. Traditionally, it depends solely on personal ...knowledge and experience of the practitioner, thereby being criticized as lacking of objectivity. Currently, no research regarding intra- and inter-agreements of automatic tongue diagnosis system (ATDS) and TCM doctors has been conducted. In this study, the ATDS is developed to extract a variety of tongue features and provide practitioners with objective information to assist diagnoses. To evaluate the ATDS clinical stability, 2 sets of tongue images taken 1 hour apart from 20 patients with possible variations in lighting and extruding tongue, are employed to investigate intra-agreement of the ATDS, intra-agreement of the TCM doctors, and the inter-agreement between the ATDS and TCM doctors. The ATDS is shown to be more consistent with significantly higher intra-agreement than the TCM doctors (kappa value: 0.93±0.06 versus 0.64±0.13) with P<0.001 (Student’s t-test). Inter-agreements between the ATDS and TCM doctors, as well as among the TCM doctors are both moderate. The high agreement of the ATDS can provide objective and reliable tongue features to facilitate doctor in making effective observation and diagnosis of specific diseases.
SPG23 is an autosomal-recessive neurodegenerative subtype of lower limb spastic paraparesis with additional diffuse skin and hair dyspigmentation at birth followed by further patchy pigment loss ...during childhood. Previously, genome-wide linkage in an Arab-Israeli pedigree mapped the gene to an approximately 25 cM locus on chromosome 1q24–q32. By using whole-exome sequencing in a further Palestinian-Jordanian SPG23 pedigree, we identified a complex homozygous 4-kb deletion/20-bp insertion in DSTYK (dual serine-threonine and tyrosine protein kinase) in all four affected family members. DSTYK is located within the established linkage region and we also found the same mutation in the previously reported pedigree and another Israeli pedigree (total of ten affected individuals from three different families). The mutation removes the last two exons and part of the 3′ UTR of DSTYK. Skin biopsies revealed reduced DSTYK protein levels along with focal loss of melanocytes. Ultrastructurally, swollen mitochondria and cytoplasmic vacuoles were also noted in remaining melanocytes and some keratinocytes and fibroblasts. Cultured keratinocytes and fibroblasts from an affected individual, as well as knockdown of Dstyk in mouse melanocytes, keratinocytes, and fibroblasts, were associated with increased cell death after ultraviolet irradiation. Keratinocytes from an affected individual showed loss of kinase activity upon stimulation with fibroblast growth factor. Previously, dominant mutations in DSTYK were implicated in congenital urological developmental disorders, but our study identifies different phenotypic consequences for a recurrent autosomal-recessive deletion mutation in revealing the genetic basis of SPG23.
Treating patients with end-stage diffuse coronary artery disease (EnD-CAD) unsuitable for coronary intervention remains a clinical challenge. They usually express refractory angina and have a high ...risk of mortality. Although growing data have indicated cell therapy is an alternative solution to medical or invasive therapy, there are still lacking useful markers to predict whether heart function will improve in the EnD-CAD patients who underwent circulatory-derived CD34+ cell therapy. By utilizing the baseline variables and results from our previous phase I/II clinical trials, the aim of this study tried to elucidate the variables predictive of the "good response" to CD34+ cell therapy. This retrospective study included 38 patients in phase I clinical trial (2011-2014), and 30 patients in phase II clinical trial (2013-2017). These patients were categorized into "good responders" and "non-responders" according to their 1-year improvement of LVEF greater than or equai to 7.0% or < 7.0% after intracoronary CD34+ cell therapy. Univariate and multivariate logistic regression models were performed to identify potential independent predictors of a good responder to cell therapy, followed by Hosmer-Lemeshow (H-L) test for goodness of fit and prediction power. Among baseline data, multivariate analysis demonstrated that the history of a former smoker was independently predictive of good responders (p = 0.006). On the other hand, male gender, the baseline Canadian Cardiovascular Society angina score greater than or equai to 3, and grades of LV diastolic dysfunction greater than or equai to 2 were significantly negative predictors of good responders (all p < 0.01). After administration of subcutaneous granulocyte-colony stimulating factor (G-CSF), a higher post-G-CSF neutrophil count in addition to the above four baseline variables also played crucial roles in early prediction of good response to CD34+ cell therapy for EnD-CAD (all p < 0.03). The H-L test displayed a good prediction power with sensitivity 83.3%, specificity 85.3%, and accuracy 84.4%. Using the results of our phase I/II clinical trials, previous smoking habit, female sex, lower grades of angina score, and diastolic dysfunction were identified to be independently predictive of "good response" to CD34+ cell therapy in the patients with EnD-CAD.
PDF
