Publications by authors named "Yanzhong Wang"

69 Publications

Survival and outcomes for stroke survivors living in care homes: a prospective cohort study.

Age Ageing 2021 Jul 6. Epub 2021 Jul 6.

Department of Population Health Sciences, School of Population Health and Environmental Sciences, King's College London, London, UK.

Background: Stroke survivors living in care homes require high levels of support with everyday living. The aims of this study were to describe the survival, health status and care received by stroke survivors living in care homes at 1-year post-stroke, compared with those in their own homes.

Methods: A total of 3,548 stroke survivors with a first ever stroke between 1998 and 2017 in the South London Stroke Register were identified for survival analysis. A total of 2,272 were included in the 1-year follow-up analysis. Cox regression and Kaplan-Meier plots were used to describe survival, stratified into four 5-year cohorts. Health status, medications and rehabilitation received at 1-year post-stroke were compared using descriptive statistics.

Results: Over the 20-year period, survival improved for stroke survivors discharged to their own home (P < 0.001) but not for those discharged to care homes (P = 0.75). Care home residents were highly disabled (median Barthel index: 6/20, interquartile range: 2-10). Rates of secondary stroke prevention medications at 1-year follow-up increased over time for care home residents, including antiplatelets from 12.3 to 38.1%, although still lower than for those in their own homes (56.3%). Speech and language problems were common in the care home population (40.0%), but only 16% had received speech and language therapy.

Conclusions: Rates of secondary stroke prevention prescribing increased over 20 years but remained lower in care home residents. The lower levels of rehabilitation received by stroke survivors in care homes, despite their higher levels of disability, suggest a gap in care and urgent need for restorative and/or preventative rehabilitation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ageing/afab140DOI Listing
July 2021

Research on Characteristic of Chronic Spontaneous Urticaria Based on Multiscale Entropy.

Comput Math Methods Med 2021 25;2021:6691356. Epub 2021 May 25.

College of Mathematical Sciences, Harbin Engineering University, Harbin 150001, China.

Chronic spontaneous urticaria (CSU) is a common skin disease which symptom is local pruritus and pain. In medicine, researchers take a certain point that the brain is the control center of CSU, but in previous experiments, the researchers found that cerebellum also had a certain effect on CSU. In order to find out the influence of CSU in the brain and cerebellum, we collected the brain resting-state fMRI data from 40 healthy controls and 32 CSU patients and used DPABI to preprocess. We calculated the entropy values of five scales by using multiscale entropy (MSE) and the average entropy values of two groups' BOLD signals; 15 regions with significant differences were found which not only had a more detailed impact in the brain but also had an impact in the cerebellum, such as precentral gyrus, lenticular putamen, and vermis of cerebellum. In addition, we found that compared with the healthy controls, the entropy values of CSU patients showed two trends which need further study. The advantage of our experiment is that the multiscale entropy value is used to get more influence regions of CSU in the brain and cerebellum. The results of this paper may provide some help for the pathological study of CSU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6691356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172304PMC
May 2021

Value of galectin-3 in the diagnosis of acute coronary syndrome and the assessment of coronary artery lesions.

Biomark Med 2021 Jun 27;15(9):647-657. Epub 2021 May 27.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

To investigate the value of galectin-3 in the diagnosis of acute coronary syndrome (ACS) and the assessment of coronary artery lesions. This study recruited 157 patients with coronary artery disease where 102 and 55 of them were subsequently grouped as ACS and non-ACS, respectively. The severity of coronary artery lesions was evaluated by Gensini score and the number of vessels involved. Receiver operator characteristics analyses of galectin-3 yielded an area under the curve of 0.679 in diagnosing ACS. The galectin-3 levels were correlated with Gensini score and the number of vessels involved. Our study demonstrated that galectin-3 is an effective auxiliary biomarker for the diagnosis of ACS and assessment of coronary artery lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/bmm-2020-0610DOI Listing
June 2021

Correction: Cullin-5 neddylation-mediated NOXA degradation is enhanced by PRDX1 oligomers in colorectal cancer.

Cell Death Dis 2021 Apr 6;12(4):369. Epub 2021 Apr 6.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03656-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024314PMC
April 2021

A multicenter randomized controlled trial indicates that paclitaxel-coated balloons provide no benefit for arteriovenous fistulas.

Kidney Int 2021 Aug 27;100(2):447-456. Epub 2021 Mar 27.

Faculty of Life Sciences and Medicine, King's College London, London, UK; Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK. Electronic address:

The role of paclitaxel-coated balloons has been established in the coronary and peripheral arterial circulations with recent interest in the use of paclitaxel-coated balloons to improve patency rates following angioplasty of arteriovenous fistulas. To assess the efficacy of paclitaxel-coated angioplasty balloons to prolong the survival time of target lesion primary patency in arteriovenous fistulas, we designed an investigator-led multi-center randomized controlled trial with follow up time variable for a minimum of one year. Patients with an arteriovenous fistula who were undergoing an angioplasty for a clinical indication were included but patients with one or more lesions outside the treatment segment were excluded. Following successful treatment with a high-pressure balloon, 212 patients were randomized. In the intervention arm, the second component was insertion of a paclitaxel-coated balloon. In the control arm, an identical procedure was followed, but using a standard balloon. The primary endpoint was time to loss of clinically driven target lesion primary patency. Primary analysis showed no significant evidence for a difference in time to end of target lesion primary patency between groups: hazard ratio 1.18 with a 95% confidence interval of 0.78 to 1.79. There were no significant differences for any secondary outcomes, including patency outcomes and adverse events. Thus, our study demonstrated no evidence that paclitaxel-coated balloons provide benefit, following standard care high-pressure balloon angioplasty, in the treatment of arteriovenous fistulas. Hence, in view of the benefit suggested by other trials, the role of paclitaxel-coated angioplasty balloons remains uncertain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2021.02.040DOI Listing
August 2021

Cullin-5 neddylation-mediated NOXA degradation is enhanced by PRDX1 oligomers in colorectal cancer.

Cell Death Dis 2021 03 12;12(3):265. Epub 2021 Mar 12.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.

NOXA, a BH3-only proapoptotic protein involved in regulating cell death decisions, is highly expressed but short-lived in colorectal cancer (CRC). Neddylated cullin-5 (CUL5)-mediated ubiquitination and degradation of NOXA is crucial to prevent its overaccumulation and maintain an appropriate action time. However, how this process is manipulated by CRC cells commonly exposed to oxidative stress remain unknown. The peroxiredoxin PRDX1, a conceivable antioxidant overexpressed in CRC tissues, has been shown to inhibit apoptosis and TRAF6 ubiquitin-ligase activity. In this study, we found that PRDX1 inhibits CRC cell apoptosis by downregulating NOXA. Mechanistically, PRDX1 promotes NOXA ubiquitination and degradation, which completely depend on CUL5 neddylation. Further studies have demonstrated that PRDX1 oligomers bind with both the Nedd8-conjugating enzyme UBE2F and CUL5 and that this tricomplex is critical for CUL5 neddylation, since silencing PRDX1 or inhibiting PRDX1 oligomerization greatly dampens CUL5 neddylation and NOXA degradation. An increase in reactive oxygen species (ROS) is not only a hallmark of cancer cells but also the leading driving force for PRDX1 oligomerization. As shown in our study, although ROS play a role in upregulating NOXA mRNA transcription, ROS scavenging in CRC cells by N-acetyl-L-cysteine (NAC) can significantly reduce CUL5 neddylation and extend the NOXA protein half-life. Therefore, in CRC, PRDX1 plays a key role in maintaining intracellular homeostasis under conditions of high metabolic activity by reinforcing UBE2F-CUL5-mediated degradation of NOXA, which is also evidenced in the resistance of CRC cells to etoposide treatment. Based on these findings, targeting PRDX1 could be an effective strategy to overcome the resistance of CRC to DNA damage-inducing chemotherapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03557-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954848PMC
March 2021

The Plasticity of Nanofibrous Matrix Regulates Fibroblast Activation in Fibrosis.

Adv Healthc Mater 2021 04 29;10(8):e2001856. Epub 2021 Jan 29.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

Natural extracellular matrix (ECM) mostly has a fibrous structure that supports and mechanically interacts with local residing cells to guide their behaviors. The effect of ECM elasticity on cell behaviors has been extensively investigated, while less attention has been paid to the effect of matrix fiber-network plasticity at microscale, although plastic remodeling of fibrous matrix is a common phenomenon in fibrosis. Here, a significant decrease is found in plasticity of native fibrotic tissues, which is associated with an increase in matrix crosslinking. To explore the role of plasticity in fibrosis development, a set of 3D collagen nanofibrous matrix with constant modulus but tunable plasticity is constructed by adjusting the crosslinking degree. Using plasticity-controlled 3D culture models, it is demonstrated that the decrease of matrix plasticity promotes fibroblast activation and spreading. Further, a coarse-grained molecular dynamic model is developed to simulate the cell-matrix interaction at microscale. Combining with molecular experiments, it is revealed that the enhanced fibroblast activation is mediated through cytoskeletal tension and nuclear translocation of Yes-associated protein. Taken together, the results clarify the effects of crosslinking-induced plasticity changes of nanofibrous matrix on the development of fibrotic diseases and highlight plasticity as an important mechanical cue in understanding cell-matrix interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202001856DOI Listing
April 2021

Procalcitonin Has Good Accuracy for Prognosis of Critical Condition and Mortality in COVID-19: A Diagnostic Test Accuracy Systematic Review and Meta-analysis.

Iran J Allergy Asthma Immunol 2020 Dec 19;19(6):557-569. Epub 2020 Dec 19.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, China.

Several reports have determined that changes in white blood cell counts and inflammatory biomarkers are related to disease outcome of coronavirus disease 2019 (COVID-19) and they can be utilized as prognostic biomarkers. For introducing a factor as a diagnostic/prognostic biomarker, diagnostic test accuracy (DTA) systematic review and meta-analysis are recommended. For the first time, we aimed to determine the accuracies of white blood cell counts and inflammatory biomarkers for prognosis of COVID-19 patient's outcome by a DTA meta-analysis. Until August24, 2020, we searched Web of Sciences, Scopus, and MEDLINE/PubMed databases to achieve related papers. Summary points and lines of included studies were calculated from 2×2 tables by bivariate/hierarchical models. Critical condition and mortality were considered as outcomes. A total of 13387 patients from 28 studies were included in this study. Six biomarkers containing leukocytosis, neutrophilia, lymphopenia, increased level of C-reactive protein, procalcitonin (PCT), and ferritin met the inclusion criteria. Analysis of the area under the curve (AUCHSROC) indicated that the PCT was the only applicable prognostic biomarker for critical condition and mortality (AUCHSROC=0.80 for both conditions). Pooled-diagnostic odds ratios were 6.78 (95% CI, 3.65-12.61) for prognosis of critical condition and 13.21 (95% CI, 3.95-44.19) for mortality. Other biomarkers had insufficient accuracies for both conditions (AUCHSROC< 0.80). Among evaluated biomarkers, only PCT has good accuracy for the prognosis of both critical condition and mortality in COVID-19 and it can be considered as a single prognostic biomarker for poor outcomes. Also, PCT has more accuracy for the prognosis of mortality in comparison to critical condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18502/ijaai.v19i6.4926DOI Listing
December 2020

Impact of multimorbidity on healthcare costs and utilisation: a systematic review of the UK literature.

Br J Gen Pract 2021 01 28;71(702):e39-e46. Epub 2020 Dec 28.

King's College London, School of Population Health Sciences, London.

Background: Managing multimorbidity is complex for both patients and healthcare systems. Patients with multimorbidity often use a variety of primary and secondary care services. Country-specific research exploring the healthcare utilisation and cost consequences of multimorbidity may inform future interventions and payment schemes in the UK.

Aim: To assess the relationship between multimorbidity, healthcare costs, and healthcare utilisation; and to determine how this relationship varies by disease combinations and healthcare components.

Design And Setting: A systematic review.

Method: This systematic review followed the bidirectional citation searching to completion method. MEDLINE and grey literature were searched for UK studies since 2004. An iterative review of references and citations was completed. Authors from all articles selected were contacted and asked to check for completeness of UK evidence. The National Institutes of Health National Heart, Lung, and Blood Institute quality assessment tool was used to assess risk of bias. Data were extracted, findings synthesised, and study heterogeneity assessed; meta-analysis was conducted when possible.

Results: Seventeen studies were identified: seven predicting healthcare costs and 10 healthcare utilisation. Multimorbidity was found to be associated with increased total costs, hospital costs, care transition costs, primary care use, dental care use, emergency department use, and hospitalisations. Several studies demonstrated the high cost of depression and of hospitalisation associated with multimorbidity.

Conclusion: In the UK, multimorbidity increases healthcare utilisation and costs of primary, secondary, and dental care. Future research is needed to examine whether integrated care schemes offer efficiencies in healthcare provision for multimorbidity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3399/bjgp20X713897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716874PMC
January 2021

Trends in prevalence of acute stroke impairments: A population-based cohort study using the South London Stroke Register.

PLoS Med 2020 10 9;17(10):e1003366. Epub 2020 Oct 9.

School of Population Health and Environmental Sciences, King's College London, London, United Kingdom.

Background: Acute stroke impairments often result in poor long-term outcome for stroke survivors. The aim of this study was to estimate the trends over time in the prevalence of these acute stroke impairments.

Methods And Findings: All first-ever stroke patients recorded in the South London Stroke Register (SLSR) between 2001 and 2018 were included in this cohort study. Multivariable Poisson regression models with robust error variance were used to estimate the adjusted prevalence of 8 acute impairments, across six 3-year time cohorts. Prevalence ratios comparing impairments over time were also calculated, stratified by age, sex, ethnicity, and aetiological classification (Trial of Org 10172 in Acute Stroke Treatment [TOAST]). A total of 4,683 patients had a stroke between 2001 and 2018. Mean age was 68.9 years, 48% were female, and 64% were White. After adjustment for demographic factors, pre-stroke risk factors, and stroke subtype, the prevalence of 3 out of the 8 acute impairments declined during the 18-year period, including limb motor deficit (from 77% [95% CI 74%-81%] to 62% [56%-68%], p < 0.001), dysphagia (37% [33%-41%] to 15% [12%-20%], p < 0.001), and urinary incontinence (43% [39%-47%) to 29% [24%-35%], p < 0.001). Declines in limb impairment over time were 2 times greater in men than women (prevalence ratio 0.73 [95% CI 0.64-0.84] and 0.87 [95% CI 0.77-0.98], respectively). Declines also tended to be greater in younger patients. Stratified by TOAST classification, the prevalence of all impairments was high for large artery atherosclerosis (LAA), cardioembolism (CE), and stroke of undetermined aetiology. Conversely, small vessel occlusions (SVOs) had low levels of all impairments except for limb motor impairment and dysarthria. While we have assessed 8 key acute stroke impairments, this study is limited by a focus on physical impairments, although cognitive impairments are equally important to understand. In addition, this is an inner-city cohort, which has unique characteristics compared to other populations.

Conclusions: In this study, we found that stroke patients in the SLSR had a complexity of acute impairments, of which limb motor deficit, dysphagia, and incontinence have declined between 2001 and 2018. These reductions have not been uniform across all patient groups, with women and the older population, in particular, seeing fewer reductions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1003366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546484PMC
October 2020

miR-204/COX5A axis contributes to invasion and chemotherapy resistance in estrogen receptor-positive breast cancers.

Cancer Lett 2020 11 3;492:185-196. Epub 2020 Aug 3.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China; Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, PR China. Electronic address:

Breast cancer is the most common cancer among women worldwide, with 70% being estrogen receptor-positive (ER+). Although ER-targeted treatment is effective in treating ER + breast cancer, chemoresistance and metastasis still prevail. Outcome-predictable biomarkers can help improve patient prognosis. Through the analysis of the Array Express database, The Cancer Genome Atlas-Breast Cancer datasets, and breast tumor tissue array results, we found that cytochrome c oxidase subunit 5a (COX5A) was related to poor prognosis of ER + breast cancer. Further studies revealed that COX5A was positively associated with metastasis and chemoresistance in ER + breast cancer. In vitro experiments showed that knockdown of COX5A was accompanied by a decrease in ERα expression, cell cycle arrest, and epithelial-mesenchymal transition blockade, resulting in an inhibition of proliferation and invasion. Knockdown of COX5A enhanced the chemosensitivity of breast cancer cells by decreasing adenosine triphosphate and increasing reactive oxygen species levels. We report that miR-204 can target and inhibit the expression of COX5A, thus, reversing the functions of COX5A in ER + breast cancer cells. We found that COX5A may serve as a prognostic biomarker in ER + breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2020.07.027DOI Listing
November 2020

Burden of Stroke in Europe: Thirty-Year Projections of Incidence, Prevalence, Deaths, and Disability-Adjusted Life Years.

Stroke 2020 08 10;51(8):2418-2427. Epub 2020 Jul 10.

School of Population Health and Environmental Sciences, King's College London, United Kingdom (H.A.W., C.D.A.W., E.E., Y.W.).

Background And Purpose: Prediction of stroke impact provides essential information for healthcare planning and priority setting. We aim to estimate 30-year projections of stroke epidemiology in the European Union using multiple modeling approaches.

Methods: Data on stroke incidence, prevalence, deaths, and disability-adjusted life years in the European Union between 1990 and 2017 were obtained from the global burden of disease study. Their trends over time were modeled using 3 modeling strategies: linear, Poisson, and exponential regressions-adjusted for the gross domestic product per capita, which reflects the impact of economic development on health status. We used the Akaike information criterion for model selection. The 30-year projections up to 2047 were estimated using the best fitting models, with inputs on population projections from the United Nations and gross domestic product per capita prospects from the World Bank. The technique was applied separately by age-sex-country groups for each stroke measure.

Results: In 2017, there were 1.12 million incident strokes in the European Union, 9.53 million stroke survivors, 0.46 million deaths, and 7.06 million disability-adjusted life years lost because of stroke. By 2047, we estimated an additional 40 000 incident strokes (+3%) and 2.58 million prevalent cases (+27%). Conversely, 80 000 fewer deaths (-17%) and 2.31 million fewer disability-adjusted life years lost (-33%) are projected. The largest increase in the age-adjusted incidence and prevalence rates are expected in Lithuania (average annual percentage change, 0.48% and 0.7% respectively), and the greatest reductions in Portugal (-1.57% and -1.3%). Average annual percentage change in mortality rates will range from -2.86% (Estonia) to -0.08% (Lithuania), and disability-adjusted life years' from -2.77% (Estonia) to -0.23% (Romania).

Conclusions: The number of people living with stroke is estimated to increase by 27% between 2017 and 2047 in the European Union, mainly because of population ageing and improved survival rates. Variations are expected to persist between countries showing opportunities for improvements in prevention and case management particularly in Eastern Europe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.029606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382540PMC
August 2020

A systematic review of machine learning models for predicting outcomes of stroke with structured data.

PLoS One 2020 12;15(6):e0234722. Epub 2020 Jun 12.

School of Population Health & Environmental Sciences, Faculty of Life Science and Medicine, King's College London, London, United Kingdom.

Background And Purpose: Machine learning (ML) has attracted much attention with the hope that it could make use of large, routinely collected datasets and deliver accurate personalised prognosis. The aim of this systematic review is to identify and critically appraise the reporting and developing of ML models for predicting outcomes after stroke.

Methods: We searched PubMed and Web of Science from 1990 to March 2019, using previously published search filters for stroke, ML, and prediction models. We focused on structured clinical data, excluding image and text analysis. This review was registered with PROSPERO (CRD42019127154).

Results: Eighteen studies were eligible for inclusion. Most studies reported less than half of the terms in the reporting quality checklist. The most frequently predicted stroke outcomes were mortality (7 studies) and functional outcome (5 studies). The most commonly used ML methods were random forests (9 studies), support vector machines (8 studies), decision trees (6 studies), and neural networks (6 studies). The median sample size was 475 (range 70-3184), with a median of 22 predictors (range 4-152) considered. All studies evaluated discrimination with thirteen using area under the ROC curve whilst calibration was assessed in three. Two studies performed external validation. None described the final model sufficiently well to reproduce it.

Conclusions: The use of ML for predicting stroke outcomes is increasing. However, few met basic reporting standards for clinical prediction tools and none made their models available in a way which could be used or evaluated. Major improvements in ML study conduct and reporting are needed before it can meaningfully be considered for practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234722PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292406PMC
September 2020

Nicotinamide N-methyltransferase inhibits autophagy induced by oxidative stress through suppressing the AMPK pathway in breast cancer cells.

Cancer Cell Int 2020 24;20:191. Epub 2020 May 24.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016 Zhejiang People's Republic of China.

Background: Nicotinamide N-methyltransferase (NNMT) is highly expressed in several cancers and can regulate cell epigenetic status and various cell metabolism pathways, such as ATP synthesis and cellular stress response. We reported in our previous papers that NNMT overexpression inhibits the apoptosis and enhances the chemotherapy resistance of breast cancer cells. This study aims to investigate the effect of NNMT on autophagy induced by oxidative stress in breast cancer cells, which might provide a novel therapeutic strategy for breast cancer treatment.

Methods: NNMT and LC3B II protein levels in the two cell models (SK-BR-3 and MDA-MB-231) with NNMT overexpression or knockdown were detected by Western blotting and correlated with each other. Changes in cellular viability, intracellular reactive oxygen species (ROS) and ATP levels were assessed after HO treatment. Then, autophagosomes were imaged by transmission electron microscopy, and LC3 puncta were examined by confocal microscopy and flow cytometry. The LC3B II level and AMPK-ULK1 pathway activity were both detected by Western blotting to determine the role of NNMT in the HO-induced autophagy.

Results: NNMT expression was negatively correlated with LC3B II expression in both cell models (SK-BR-3 and MDA-MB-231). Then, NNMT overexpression attenuated the autophagy induced by HO in SK-BR-3 cells, whereas knockdown promoted autophagy induced by HO in MDA-MB-231 cells. Furthermore, mechanistic studies showed that NNMT suppressed the ROS increase, ATP decrease and AMPK-ULK1 pathway activation, resulting in the inhibition of HO-induced autophagy in breast cancer cells.

Conclusions: We conclude that NNMT inhibits the autophagy induced by oxidative stress through the ROS-mediated AMPK-ULK1 pathway in breast cancer cells and may protect breast cancer cells against oxidative stress through autophagy suppression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-020-01279-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247246PMC
May 2020

Hyaluronic acid predicts poor prognosis in breast cancer patients: A protocol for systematic review and meta analysis.

Medicine (Baltimore) 2020 May;99(22):e20438

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou.

Background: Hyaluronic acid (HA) may be a novel prognostic biomarker of breast cancer. However, the available evidence is controversial. Therefore, we performed a meta-analysis to determine the prognostic role of HA in breast cancer.

Methods: The data were extracted from seven articles by searching the databases of PubMed, EMBASE, Web of Science, the Chinese National Knowledge Infrastructure and Wanfang data for the prognostic role of HA in breast cancer. In reference to survival outcomes, the pooled hazard ratios (HRs) of HA were calculated given a 95% confidence interval (CI).

Results: A total of seven articles were included in our study involving 2664 cases. The result of meta-analysis showed that a high HA level predicts poor overall survival (OS) (HR = 1.86, 95% CI: 1.28-2.71, P = .001) and shortened disease-free or recurrence-free survival or progression free survival (DFS/RFS/PFS) (HR = 1.63, 95% CI: 1.14-2.33, P = .007) in breast cancer patients. Moreover, a high HA level in stroma (HR = 1.63, 95% CI: 1.06-2.51, P = .025) and plasma (HR = 3.26, 95% CI: 2.25-4.73, P < .001) significantly predicted poor OS. Besides, a tendency shows that HA was significantly correlated with lymph node metastasis (HR = 1.55, 95% CI: 0.96-2.49, P = .070) and tumor grade (HR = 2.10, 95% CI: 0.89-4.96, P = .089) on the clinical characteristics of patients.

Conclusion: These results suggested that HA has a potential to be prognostic biomarker in breast cancer patients, especially location in stroma and plasma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000020438DOI Listing
May 2020

Identification of Ala2Thr mutation in insulin gene from a Chinese MODY10 family.

Mol Cell Biochem 2020 Jul 13;470(1-2):77-86. Epub 2020 May 13.

Shanghai Diabetes Institute, Department of Endocrinology & Metabolism, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.

More than 80% of maturity-onset diabetes of the young (MODY) in Chinese is genetically unexplained. To investigate whether the insulin gene (INS) mutation is responsible for some Chinese MODY, we screened INS mutations causing MODY10 in MODY pedigrees and explored the potential pathogenic mechanisms. INS mutations were screened in 56 MODY familial probands. Structure-function characterization and clinical profiling of identified INS mutations were conducted. An INS mutation, at the position 2 alanine-to-threonine substitution (A2T), was identified and co-segregated with hyperglycemia in a MODY pedigree. The A2T mutation converted an α-helix into a β-sheet at the N-terminal of the signal peptide (SP) of preproinsulin. The A2T mutation did not affect preproinsulin translocation across endoplasmic reticulum (ER) membrane, but impaired its SP cleavage within the ER. In INS-1 cells transfected with an A2T mutant, glucose-stimulated insulin secretion (GSIS) was significantly decreased, while BiP luciferase activities were significantly increased compared to that of wild type (WT). We identified an INS-A2T mutation cosegregating with diabetes in a Chinese MODY pedigree. This mutation severely impaired SP cleavage and thus blocked the formation of proinsulin, resulting in enhanced ER stress, which may be responsible for decreased insulin secretion and subsequently, the onset of MODY10.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-020-03748-0DOI Listing
July 2020

Long-term trends in death and dependence after ischaemic strokes: A retrospective cohort study using the South London Stroke Register (SLSR).

PLoS Med 2020 03 12;17(3):e1003048. Epub 2020 Mar 12.

School of Population Health and Environmental Sciences, King's College London, London, United Kingdom.

Background: There have been reductions in stroke mortality over recent decades, but estimates by aetiological subtypes are limited. This study estimates time trends in mortality and functional dependence by ischaemic stroke (IS) aetiological subtype over a 16-year period.

Methods And Findings: The study population was 357,308 in 2011; 50.4% were males, 56% were white, and 25% were of black ethnic backgrounds. Population-based case ascertainment of stroke was conducted, and all participants who had their first-ever IS between 2000 and 2015 were identified. Further classification was concluded according to the underlying mechanism into large-artery atherosclerosis (LAA), cardio-embolism (CE), small-vessel occlusion (SVO), other determined aetiologies (OTH), and undetermined aetiologies (UND). Temporal trends in survival rates were examined using proportional-hazards survival modelling, adjusted for demography, prestroke risk factors, case mix variables, and processes of care. We carried out additional regression analyses to explore patterns in case-fatality rates (CFRs) at 30 days and 1 year and to explore whether these trends occurred at the expense of greater functional dependence (Barthel Index [BI] < 15) among survivors. A total of 3,128 patients with first-ever ISs were registered. The median age was 70.7 years; 50.9% were males; and 66.2% were white, 25.5% were black, and 8.3% were of other ethnic groups. Between 2000-2003 and 2012-2015, the adjusted overall mortality decreased by 24% (hazard ratio [HR] per year 0.976; 95% confidence interval [CI] 0.959-0.993). Mortality reductions were equally noted in both sexes and in the white and black populations but were only significant in CE strokes (HR per year 0.972; 95% CI 0.945‒0.998) and in patients aged ≥55 years (HR per year 0.975; 95% CI 0.959‒0.992). CFRs within 30 days and 1 year after an IS declined by 38% (rate ratio [RR] per year 0.962; 95% CI 0.941‒0.984) and 37% (RR per year 0.963; 95% CI 0.949‒0.976), respectively. Recent IS was independently associated with a 23% reduced risk of functional dependence at 3 months after onset (RR per year 0.983; 95% CI 0.968-0.998; p = 0.002 for trend). The study is limited by small number of events in certain subgroups (e.g., LAA), which could have led to insufficient power to detect significant trends.

Conclusions: Both mortality and 3-month functional dependence after IS decreased by an annual average of around 2.4% and 1.7%, respectively, during 2000‒2015. Such reductions were particularly evident in strokes of CE origins and in those aged ≥55 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1003048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067375PMC
March 2020

Combining serum calcitonin, carcinoembryonic antigen, and neuron-specific enolase to predict lateral lymph node metastasis in medullary thyroid carcinoma.

J Clin Lab Anal 2020 Jul 6;34(7):e23278. Epub 2020 Mar 6.

Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: This study aimed to investigate the clinical application of combined detection of serum calcitonin (Ctn), carcinoembryonic antigen (CEA), and neuron-specific enolase (NSE) in predicting lateral lymph node metastasis (LLNM) in medullary thyroid carcinoma (MTC).

Methods: Seventy-four consecutive patients with MTC were enrolled. The relationship between serum Ctn, CEA, and NSE and LLNM was retrospectively analyzed by univariate analysis and logistic regression analysis. Furthermore, the clinical application of serum Ctn, CEA, and NSE combined detection in prediction of LLNM in MTC was also evaluated.

Results: The rate of LLNM in this study was 48.64% (36/74).The expression levels of serum Ctn, CEA, and NSE in MTC with LLNM were significantly higher than those without LLNM (all P < .01). The area under the curve (AUC) predicted by serum Ctn, CEA, and NSE for LLNM in MTC patients was 0.867, 0.831, and 0.726, respectively, and the AUC of serum Ctn, CEA, and NSE combined detection was up to 0.890, higher than using a single biomarker. The sensitivity and specificity of serum Ctn, CEA, and NSE combined detection in prediction of LLNM were 88.89% and 81.57%, respectively.

Conclusions: The concentrations of serum Ctn, CEA, and NSE are closely related to LLNM in MTC, and the combined detection of all three biomarkers has a higher clinical value in the evaluation of MTC patients with LLNM. With more perspective study in the future, it would be an indicator of influencing personalized surgical strategy for different MTC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.23278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370728PMC
July 2020

Long-Term Trends in Stroke Survivors Discharged to Care Homes: The South London Stroke Register.

Stroke 2020 01 6;51(1):179-185. Epub 2019 Nov 6.

From the Department of Population Health Sciences, School of Population Health and Environmental Sciences (A.C., A. Bhalla, A.B., L.E.S., I.M., C.M., A.R., C.S., F.C.M., C.W., Y.W.), King's College London, United Kingdom.

Background and Purpose- Care homes provide care to many stroke survivors, yet little is known about changes in care home use over time. We aim to determine trends in discharge to care homes, to explore the characteristics of stroke survivors over time (1995-2018), and to identify the associations between these characteristics and discharge to care homes poststroke. Methods- Using data from the South London Stroke Register between 1995 and 2018, we estimated the proportions discharged to care homes and their characteristics over time, assessed by tests for trends. Multivariable logistic regression models were built to assess the associations between their characteristics and discharge destination. Results- Of 4172 stroke survivors, 484 (12%) were discharged to care homes. This proportion has decreased from 24% in 1995 to 2000 to 5% in 2013 to 2018. The mean age of those discharged to care homes has increased over time, from 73 to 75 (<0.001). Among stroke survivors discharged to a care home, the proportion with a prestroke Barthel Index <15 has also increased over time from 7% to 21% (=0.027), while the proportion with a 7-day poststroke Barthel Index <15 remains largely unchanged over time (93% in 1995-2000, 90% in 2013-2018). The characteristics most strongly associated with discharge to care homes were (odds ratio [95% CI]) age (1.05 [1.04-1.07] per year), stroke subtype (hemorrhagic; 0.64 [0.43-0.95]), stroke severity (Glasgow Coma Scale score, <13; 1.67 [1.19-2.35]), failed swallow test at admission (1.65 [1.20-2.25]), 7-day poststroke Barthel Index <15 (3.58 [2.20-6.03]), and a longer hospital stay (1.02 [1.02-1.03] per day). Conclusions- Over >20 years, there has been an 80% reduction in the proportion of stroke survivors discharged to care homes, influenced by changes in the demographics, disability, and stroke care in the underlying stroke population. In those moving to care homes, the level of poststroke disability remains high, requiring continued attention and investment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.119.026618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924949PMC
January 2020

Chiral geometry regulates stem cell fate and activity.

Biomaterials 2019 11 26;222:119456. Epub 2019 Aug 26.

The Stomatologic Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. Electronic address:

Geometry sensing of cells inevitably involves cytoskeletal remodeling and the activation of biochemical signaling, which control multiple aspects of cell behaviors, such as proliferation, differentiation and migration. A variety of size-, shape- and geometry-dependent cell behaviors have been revealed, but the role of geometric chirality in regulating cellular behaviors and the underlying biophysical mechanisms remain elusive. Here, we report an intriguing mechanotransduction of stem cells on chiral geometries that human mesenchymal stem cells (hMSCs) prefer to migrate towards dextral geometry with nearly 30% relative advantage in migration speed, referred to as "chirotaxis". We also found that cell adhesion, proliferation, and differentiation of hMSCs are greatly enhanced for cells cultured on dextral geometry than those on sinistral geometry, by triggering transcription factor AP-1 complex through p38/MAPK signaling that regulates hMSCs fate and activity. We demonstrated that the cytoskeletal network consisting of transverse and radial stress fibers exhibits a strengthening/offsetting effect on dextral/sinistral geometry through focal adhesion sites, and consequently, cell's cytoskeletal contractility on the dextral geometry is nearly 80% higher. These findings highlight the importance of geometric chirality as an extracellular cue in regulating stem cell's behaviors through cell-material interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2019.119456DOI Listing
November 2019

Effect of combined testing of ceramides with high-sensitive troponin T on the detection of acute coronary syndrome in patients with chest pain in China: a prospective observational study.

BMJ Open 2019 07 26;9(7):e028211. Epub 2019 Jul 26.

Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Shanghai, China.

Objective: Ceramides are associated with coronary plaque vulnerability. We aim to investigate the potential diagnostic value of ceramides for acute coronary syndrome (ACS) in Chinese patients with chest pain.

Design: Prospective observational survey.

Setting: Shanghai, China, 2016-2017.

Participants: A total of 2773 patients with chest pain from four hospitals in Shanghai, China, between August 2016 and October 2017.

Main Outcome Measures: Performance of metabolites model in detection of ACS cases including ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina.

Results: Plasma levels of 12 ceramide molecules and corresponding ratios were compared between patients diagnosed with ACS and those without. Cer(d18:1/24:1(15Z))/Cer(d18:1/24:0) ratio, Cer(d18:1/14:0) and Cer(d18:1/22:0) were independent predictors of ACS after adjustment of traditional risk factors and high-sensitivecardiac troponin T. Receiver operating characteristic curve analysis showed a significant improvement in detecting ACS in the multivariable model with ceramides compared with that without (0.865 (0.840 to 0.889) vs 0.808 (0.776 to 0.841), p<0.001).

Conclusion: Distinct plasma ceramides are independent diagnostic predictors of ACS among patients with chest pain. Ceramides together with high-sensitive troponin and traditional factors showed great potential in identifying ACS among patients with chest pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2018-028211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661622PMC
July 2019

Reversal of EGFR inhibitors' resistance by co-delivering EGFR and integrin αvβ3 inhibitors with nanoparticles in non-small cell lung cancer.

Biosci Rep 2019 08 28;39(8). Epub 2019 Aug 28.

Department of Pneumology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, 318 Chaowang Road, Hangzhou 310005, Zhejiang, China

Tumor cells, with drug resistance, are associated with failed treatment and poor prognosis. Our aim was to explore potential strategy to overcome the epidermal growth factor receptor (EGFR) inhibitors resistance in non-small cell lung cancer (NSCLC). Flow cytometry was used to examine and sort cells. Using MTT assay, we detected the cell viability under different conditions. Using RT-qPCR and Western blot, we determined the targeted gene expression in mRNA and protein levels. The morphology of the prepared nanoparticles was pictured by transmission electron microscopy. We also performed immunohistochemistry (IHC) and immunofluorescence (IF) to detect the proteins expression. Subcutaneous cancer models in nude mice were constructed to evaluate the anti-cancer effects : Here, we observed enhanced expression of integrin αvβ3 in tumor tissues from EGFR inhibitors resistant patients. Also, integrin αvβ3-positive NSCLC cells revealed significant EGFR inhibitors resistance, resulting from the activation of Galectin-3/KRAS/RalB/TBK1/NF-κB signaling pathway. Co-encapsulating integrin αvβ3 inhibitor and EGFR inhibitor further improved the drug delivery system, leading to superior anti-cancer effects and reduced systemic toxicity. Our results demonstrated that co-encapsulation of erlotinib and cilengitide by MPEG-PLA (Erlo+Cilen/PP) nanoparticles revealed enhanced tumor suppression along with reduced organ damages, providing an innovative approach for NSCLC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BSR20181259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712436PMC
August 2019

Nicotinamide N-methyltransferase enhances chemoresistance in breast cancer through SIRT1 protein stabilization.

Breast Cancer Res 2019 05 17;21(1):64. Epub 2019 May 17.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China.

Background: Nicotinamide N-methyltransferase (NNMT) is overexpressed in various human tumors and involved in the development and progression of several carcinomas. In breast cancer, NNMT was found to be overexpressed in several cell lines. However, the clinical relevance of NNMT in breast cancer is not yet clear.

Methods: NNMT expression in breast carcinoma was examined by immunohistochemistry, and then, its relationship with patient clinicopathological characteristics was analyzed. The effects of NNMT on chemoresistance in breast cancer cells were assessed by cell viability, colony formation, and apoptosis assay. The NNMT, SIRT1, p53, and acetyl-p53 proteins, which are involved in NNMT-related chemoresistance, were examined by Western blotting. The SIRT1 mRNA was examined by real-time PCR, and its activity was measured by using the SIRT1 deacetylase fluorometric reagent kit.

Results: NNMT expression was significantly higher (53.9%) in breast carcinoma than in paracancerous tissues (10.0%) and breast hyperplasia (13.3%). A high level of NNMT expression correlated with poor survival and chemotherapy response in breast cancer patients who received chemotherapy. Ectopic overexpression of NNMT significantly inhibited the apoptotic cell death and suppression of colony formation induced by adriamycin and paclitaxel. Mechanistic studies revealed that NNMT overexpression increased SIRT1 expression and promoted its activity. Either inhibition of SIRT1 by EX527 or knockdown of SIRT1 by siRNA could reverse NNMT-mediated resistance to adriamycin and paclitaxel, which suggests that SIRT1 plays a critical role in NNMT-related chemoresistance in breast cancer.

Conclusions: The results of this study demonstrate a novel correlation between the NNMT expression level and patient survival, suggesting that NNMT has the potential to become a new prognostic biomarker to predict the treatment outcomes of the clinical chemotherapy in breast cancer. Moreover, targeting NNMT or downstream SIRT1 may represent a new therapeutic approach to improve the efficacy of breast cancer chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-019-1150-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525439PMC
May 2019

A seleno-hormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicities.

PLoS One 2019 29;14(4):e0205626. Epub 2019 Apr 29.

Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.

2,2'-diselenyldibenzoic acid (DSBA) is a chemical probe produced to explore the pharmacological properties of diphenyldiselenide-derived agents with seleno-hormetic activity undergoing preclinical development. The present study was designed to verify in vivo the drug's properties and to determine mechanistically how these may mediate the protection of tissues against stress conditions, exemplified by ionizing radiation induced damage in mouse bone marrow. In murine bone marrow hematopoietic cells, the drug initiated the activation of the Nrf2 transcription factor resulting in enhanced expression of downstream stress response genes. This type of response was confirmed in human liver cells and included enhanced expression of glutathione S-transferases (GST), important in the metabolism and pharmacological function of seleno-compounds. In C57 BL/6 mice, DSBA prevented the suppression of bone marrow hematopoietic cells caused by ionizing radiation exposure. Such in vivo prevention effects were associated with Nrf2 pathway activation in both bone marrow cells and liver tissue. These findings demonstrated for the first time the pharmacological properties of DSBA in vivo, suggesting a practical application for this type of Se-hormetic molecules as a radioprotective and/or prevention agents in cancer treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205626PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488049PMC
December 2019

Template-ready PCR method for detection of human telomerase reverse transcriptase mRNA in sputum.

Anal Biochem 2019 07 13;577:34-41. Epub 2019 Apr 13.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, PR China. Electronic address:

Human telomerase reverse transcriptase (hTERT) mRNA in tissue is a biomarker of lung cancer, but hTERT mRNA in sputum had not been successfully detected with conventional reverse transcription PCR methods. Here, we developed a novel PCR protocol: Template-Ready PCR (TRPCR), to detect sputum hTERT mRNA, in which probes serve as templates of amplification. While free probes and dsDNA were removed in template preparation through aspiration and restriction digestion, probes that formed into heterocomplex with target RNA remained intact for PCR amplification. By fishing out the heterocomplex and amplifying the probes, TRPCR achieved sensitivity higher than reverse transcription-quantitative PCR (RT-qPCR). ROC curve of sputum hTERT mRNA by TRPCR assay showed the discrimination in high sensitivity and specificity between patients with lung cancer and lung cancer-free donors at the PCR Ct cutoff of 33. We further validated this approach through TRPCR assay of sputum from 858 lung cancer patients and 480 non-malignant pulmonary disease patients. 722 (84.2%) cases from 858 with lung cancer patients were detected as positive, whereas 461 (96.0%) cases from 480 non-malignant pulmonary disease patients were detected as negative, suggesting that TRPCR assay of sputum hTERT mRNA can serve as a non-invasive molecular diagnosis of lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ab.2019.04.008DOI Listing
July 2019

Nitrogen-doped carbon dots encapsulated in the mesoporous channels of SBA-15 with solid-state fluorescence and excellent stability.

Nanoscale 2019 Apr;11(15):7247-7255

North University of China, School of Energy and Power Engineering & School of Materials Science and Engineering, Xueyuan Road 3, Taiyuan 030051, China.

A simple and low-cost approach is developed, by which nitrogen-doped carbon dots (NCDs) with a negative potential are assembled inside the mesoporous channels of SBA-15 via capillary force. The unique confined microenvironment leads to a strong interaction between confined NCDs and the inner surface of SBA-15, thus effectively avoiding the aggregation of NCDs. The resultant composite (NCDs-in-SBA-15) exhibits blue fluorescence similar to the NCD aqueous solution, and shows excellent structural, thermal and photostability. Solid NCDs-in-SBA-15 still emits fluorescence even after heat treatment at 400 °C under ambient atmosphere. In addition, NCDs-in-SBA-15 possesses remarkable resistance to acid/alkali solvents. Furthermore, NCDs-in-SBA-15 shows superior selectivity and adsorption capacity to Fe3+. The facile approach and these advantageous performances could make CDs meet the requirements of fluorescent materials in the solid state and then have wider applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9nr01224aDOI Listing
April 2019

Factors, trends, and long-term outcomes for stroke patients returning to work: The South London Stroke Register.

Int J Stroke 2019 10 15;14(7):696-705. Epub 2019 Mar 15.

Guy's and St Thomas' NHS Foundation Trust, London, UK.

Background And Purpose: There is limited information on factors, trends, and outcomes in return to work at different time-points post-stroke; this study aims to identify these in a multi-ethnic urban population.

Methods: Patterns of return to work were identified in individuals in paid work prior to first-ever stroke in the population-based South London Stroke Register (SLSR) between 1995 and 2014. Multivariable logistic regression examined associations between patient characteristics and return to work at 1 year (1 y), 5 years (5 y) and 10 years (10 y) post-stroke.

Results: Among 5609 patients, 940 (17%) were working prior to their stroke, of whom 177 (19%) were working 3 months post-stroke, declining to 172 (18%) at 1 y, 113 (12%) at 5 y, and 27 (3%) at 10 y. Factors associated with return to work within 1 y, after logistic regression, included functional independence (BI ≥ 19;  < 0.01) and shorter length of stay ( < 0.05). Younger age ( < 0.01) was associated with return to work at 5 y and 10 y post-stroke. Non-manual occupation ( < 0.05) was associated with return to work at 10 y post-stroke. Return to work within 1 y increased the likelihood of working at 5 y (OR: 13.68; 95% CI 5.03-37.24) and 10 y (9.07; 2.07-39.8). Of those who were independent at follow-up (BI ≥ 19), 48% were working at 1 y, 42% at 5 y, and 28% at 10 y. Lower rates of anxiety and depression and higher self-rated health were associated with return to work at 1 y ( < 0.01).

Conclusion: Although functionally independent stroke survivors are more likely to return to work long-term, a large proportion do not return to work despite functional independence. Return to work post-stroke is associated with improved long-term psychological outcomes and quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493019832997DOI Listing
October 2019

Long-term trends in incidence and risk factors for ischaemic stroke subtypes: Prospective population study of the South London Stroke Register.

PLoS Med 2018 10 5;15(10):e1002669. Epub 2018 Oct 5.

School of Population Health and Environmental Sciences, King's College London, London, United Kingdom.

Background: As the average life expectancy increases, more people are predicted to have strokes. Recent studies have shown an increasing incidence in certain types of cerebral infarction. We aimed to estimate time trends in incidence, prior risk factors, and use of preventive treatments for ischaemic stroke (IS) aetiological subtypes and to ascertain any demographic disparities.

Methods And Findings: Population-based data from the South London Stroke Register (SLSR) between 2000 and 2015 were studied. IS was classified, based on the underlying mechanism, into large-artery atherosclerosis (LAA), cardio-embolism (CE), small-vessel occlusion (SVO), other determined aetiologies (OTH), and undetermined aetiologies (UND). After calculation of age-, sex-, and ethnicity-specific incidence rates by subtype for the 16-year period, we analysed trends using Cochran-Armitage tests, Poisson regression models, and locally estimated scatterplot smoothers (loess). A total of 3,088 patients with first IS were registered. Between 2000-2003 and 2012-2015, the age-adjusted incidence of IS decreased by 43% from 137.3 to 78.4/100,000/year (incidence rate ratio [IRR] 0.57, 95% CI 0.5-0.64). Significant declines were observed in all subtypes, particularly in SVO (37.4-18; p < 0.0001) and less in CE (39.3-25; p < 0.0001). Reductions were recorded in males and females, younger (<55 years old) and older (≥55 years old) individuals, and white and black ethnic groups, though not significantly in the latter (144.6-116.2; p = 0.31 for IS). A 4-fold increase in prior-to-stroke use of statins was found (adjusted odds ratio [OR] 4.39, 95% CI 3.29-5.86), and despite the increasing prevalence of hypertension (OR 1.54, 95% CI 1.21-1.96) and atrial fibrillation (OR 1.7, 95% CI 1.22-2.36), preventive use of antihypertensive and antiplatelet drugs was declining. A smaller number of participants in certain subgroup-specific analyses (e.g., black ethnicity and LAA subtype) could have limited the power to identify significant trends.

Conclusions: The incidence of ISs has been declining since 2000 in all age groups but to a lesser extent in the black population. The reported changes in medication use are unlikely to fully explain the reduction in stroke incidence; however, innovative prevention strategies and better management of risk factors may contribute further reduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1002669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173399PMC
October 2018

Insights into pathogenesis of five novel GCK mutations identified in Chinese MODY patients.

Metabolism 2018 12 23;89:8-17. Epub 2018 Sep 23.

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

Objective: Heterozygous inactivating mutations in GCK are associated with defects in pancreatic insulin secretion and/or hepatic glycogen synthesis leading to mild chronic hyperglycaemia of maturity onset diabetes of young type 2 (MODY2). However, the effect of naturally occurring GCK mutations on the pathogenesis for MODY2 hyperglycaemia remains largely unclear, especially in the Asian population. The aim of this study is to explore the potential pathogenicity of novel GCK mutations related to MODY2.

Methods: Genetic screening for GCK mutations from 96 classical MODY families was performed, and structure-function characterization and clinical profile of identified GCK mutations were conducted.

Results: Five novel (F195S, I211T, V222D, E236G and K458R) and five known (T49N, I159V, R186X, A188T and M381T) mutations were identified and co-segregated with hyperglycaemia in their pedigrees. R186X generates non-functional truncated form and V222D and E236G fully inactivate glucokinase due to severe structure disruptions. The other seven GCK mutations exhibited marked reductions in catalytic efficiency and thermo-stability; notably, the interaction with GKRP was significantly enhanced in I211T, I159V, T49N and K458R, reduced in F195S and M381T, and completely lost with A188T. 31% (17/55) of MODY2 patients showed signs of insulin resistance. Conventional hypoglycaemia treatment did not improve the HbA1C in MODY2 patients when insulin resistance is not present.

Conclusions: Five novel GCK mutations have been identified in Chinese MODY. The defects in enzymatic activity and protein stability, together with alteration of GKRP binding on GCK mutants may synergistically contribute to the development of MODY2 hyperglycaemia. No treatment should be prescribed to MODY2 patients when insulin resistance is not present.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2018.09.004DOI Listing
December 2018

Cross-Linked Nanohybrid Polymer Electrolytes With POSS Cross-Linker for Solid-State Lithium Ion Batteries.

Front Chem 2018 25;6:186. Epub 2018 May 25.

State Key Laboratory of Powder Metallurgy, Central South University, Changsha, China.

A new class of freestanding cross-linked hybrid polymer electrolytes (HPEs) with POSS as the cross-linker was prepared by a one-step free radical polymerization reaction. Octavinyl octasilsesquioxane (OV-POSS) with eight functional corner groups was used to provide cross-linking sites for the connection of polymer segments and the required mechanical strength to separate the cathode and anode. The unique cross-linked structure offers additional free volume for the motion of EO chains and provides fast and continuously interconnected ion-conducting channels along the nanoparticles/polymer matrix interface. The HPE exhibits the highest ionic conductivity of 1.39 × 10 S cm, as well as excellent interfacial compatibility with the Li electrode at 80°C. In particular, LiFePO/Li cells based on the HPE deliver good rate capability and long-term cycling performance with an initial discharge capacity of 152.1 mAh g and a capacity retention ratio of 88% after 150 cycles with a current density of 0.5 C at 80°C, demonstrating great potential application in high-performance LIBs at elevated temperatures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2018.00186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981318PMC
May 2018
-->